Search CTL/CD8+ T-Cell Epitope Database

Found 47 matching records:

Displaying record number 60274

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Species (MHC/HLA)	human(A*30)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
SPAIFQSSM had a significantly positive association with HLA A*30; it was recognized by 5/46 A*30-positive subjects and 5/232 A*30-negative subjects.

References

Pereyra2014 Florencia Pereyra, David Heckerman, Jonathan M. Carlson, Carl Kadie, Damien Z. Soghoian, Daniel Karel, Ariel Goldenthal, Oliver B. Davis, Charles E. DeZiel, Tienho Lin, Jian Peng, Alicja Piechocka, Mary Carrington, and Bruce D. Walker. HIV Control Is Mediated in Part by CD8+ T-Cell Targeting of Specific Epitopes. J. Virol., 88(22):12937-12948, Nov 2014. PubMed ID: 25165115. Show all entries for this paper.

Displaying record number 60277

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Species (MHC/HLA)	human(A*6802)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
SPAIFQSSM had a significantly positive association with HLA A*6802; it was recognized by 1/9 A*6802-positive subjects and 0/189 A*6802-negative subjects.

References

Displaying record number 56388

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(156-164)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	escape, HLA associated polymorphism

Notes

98 newly infected patients were studied to track early host HLA and Gag/Pol/Nef epitope immune responses' association with viral evolution. Response hierarchies were the same as those for later infection, and 50% of the most rapidly substituting epitopes were restricted by protective HLA, e.g. Gag B*57-associated mutations which were the most rapidly reverting upon transmission to a non-B*57-host. While there are great differences in mutation rates and reversions across the HIV proteome, most early viral change is driven by immune pressure.
HLA-driven epitope evolution was seen in 80% of published CTL epitopes.
HLAs-B*07-associated substitution within optimally defined epitope SPAIFQSSM is at position S7, SPAIFQsSM. SM9 recognition frequency is ~20% and escape occurs at >3 months post-infection.

References

Brumme2008 Zabrina L. Brumme, Chanson J. Brumme, Jonathan Carlson, Hendrik Streeck, Mina John, Quentin Eichbaum, Brian L Block, Brett Baker, Carl Kadie, Martin Markowitz, Heiko Jessen, Anthony D. Kelleher, Eric Rosenberg, John Kaldor, Yuko Yuki, Mary Carrington, Todd M. Allen, Simon Mallal, Marcus Altfeld, David Heckerman, and Bruce D. Walker. Marked Epitope- and Allele-Specific Differences in Rates of Mutation in Human Immunodeficiency Type 1 (HIV-1) Gag, Pol, and Nef Cytotoxic T-Lymphocyte Epitopes in Acute/Early HIV-1 Infection. J. Virol., 82(18):9216-9227, Sep 2008. PubMed ID: 18614631. Show all entries for this paper.

Displaying record number 60272

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
SPAIFQSSM had a significantly positive association with HLA B*07; it was recognized by 19/38 B*07-positive subjects and 14/303 B*07-negative subjects.

References

Displaying record number 59136

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	elite controllers

Notes

In a follow-up on the anonymous 1999 Berlin patient (not Timothy Brown of 2008), viral replication suppression was seen after 15 years of absence of ART. Half the HIV-specific CTL responses in this patient were restricted by HLA-B*57, with the most immunodominant being against Nef HW9, HTQGYFPDW.
Patient autologous sequence of B*07-restricted RT SM9, SPAIFQSSM, elicited a CTL response of >1000 sfu/10<sup>6</sup> PBMC when tested by EliSpot.

References

Jessen2014 Heiko Jessen, Todd M. Allen, and Hendrik Streeck. How a Single Patient Influenced HIV Research — 15-Year Follow-Up. N. Engl. J. Med., 370(7):682-683, 13 Feb 2014. PubMed ID: 24521131. Show all entries for this paper.

Displaying record number 59006

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	Pol311
Subtype	A
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection, vaccine
Patient MHC/HLA	P2: A6802, A7401, B3501, B5301; P7: A2601, A6801, B*0801
Country	Guinea-Bissau
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses, vaccine antigen design

Vaccine Details

Vaccine type	peptide
Vaccine strain	A clade
Adjuvant	CAF01

Notes

Therapeutic vaccination of chronically infected HIV-1 subjects was evaluated as a means of halting disease progression. A subdominant peptide vaccine containing 15 CTL epitopes and 3 helper T-cell peptides along with an adjuvant was delivered to 18 infected subjects. Using IFN-γ EliSpot, 9 new T-cell responses were detected in 6/14 subjects whose viral loads (VL) remained stable. 7/10 CTL and other pre-existing responses, however, were not significantly detected.
Pol311, SPRTLNAWV, is a CTL epitope sequence used as a vaccine component.

References

Roman2013 Victor Raúl Gómez Román, Kristoffer Jarlov Jensen, Sanne Skov Jensen, Christian Leo-Hansen, Sanne Jespersen, David da Silva Té, Candida Medina Rodrigues, Christoph Mikkel Janitzek, Lasse Vinner, Terese Lea Katzenstein, Peter Andersen, Ingrid Kromann, Lars Vibe Andreasen, Ingrid Karlsson, and Anders Fomsgaard. Therapeutic Vaccination Using Cationic Liposome-Adjuvanted HIV Type 1 Peptides Representing HLA-Supertype-Restricted Subdominant T Cell Epitopes: Safety, Immunogenicity, and Feasibility in Guinea-Bissau. AIDS Res Hum Retroviruses, 29(11):1504-1512, Nov 2013. PubMed ID: 23634822. Show all entries for this paper.

Displaying record number 57795

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction, HLA associated polymorphism

Notes

From a large study of HLA-associated polymorphisms, 431 putative epitopes with good EpiPred scores were selected; 320 of these were tested for IFNgamma EliSpot responses in subjects carrying the predicted HLA.
Peptides with response rate >40% (comparable with mean response rate of 33% for known epitopes) and tested in 5 or more individuals with respective HLA were considered in this study as probable novel epitopes and entered in the database. 41 additional "possible" novel epitopes for which either <5 individuals were tested or response rate was below 40%, are not entered in the database.
There was a markedly higher proportion of putative epitopes in Nef, and the Nef epitopes tended to have the most high-magnitude EliSpot responses. Among 33 epitopes that elicited a response in over 40% out of 5 or more individuals tested, over 61% clustered in Nef.
Epitope SPAIFQSSM was recognized by 7/11 B*07-positive HIV-1-infected patients.

References

Almeida2011 Coral-Ann M. Almeida, Corine Bronke, Steven G. Roberts, Elizabeth McKinnon, Niamh M. Keane, Abha Chopra, Carl Kadie, Jonathan Carlson, David W. Haas, Sharon A. Riddler, Richard Haubrich, David Heckerman, Simon Mallal, and Mina John. Translation of HLA-HIV Associations to the Cellular Level: HIV Adapts to Inflate CD8 T Cell Responses against Nef and HLA-Adapted Variant Epitopes. J. Immunol., 187(5):2502-2513, 1 Sep 2011. PubMed ID: 21821798. Show all entries for this paper.

Displaying record number 57321

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	A, CRF02_AG, CRF06_cpx, CRF09_cpx
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	Burkina Faso
Experimental methods	Other
Keywords	drug resistance

Notes

Drug-associated mutations were analyzed in HIV-1 pol gene from drug-naive patients in Burkina Faso. 12.5% of all mutations were drug resistance-associated, suggesting either transmission from an ART-treated tramsitter or prior undocumented use of ART by the subject. Subtype specific polymorphisms were also seen, some of them within CTL epitopes.
B-consensus HLA-B*07-restricted epitope SPAIFQSSM was found in subtype CRF02.AG and CRF09.cpx sequences as SPAIFQaSM, but variant SPAIFQhSM was seen in subtype A. 8% Burkinabe carry HLA-B*7.

References

Tebit2009 Denis M. Tebit, Lassana Sangaré, Fabrice Tiba, Yameogo Saydou, Aline Makamtse, Hermann Somlare, Guillaume Bado, Boris G. Kouldiaty, Inoussa Zabsonre, Sibiri L. Yameogo, Kanokporn Sathiandee, Joseph Y. Drabo, and Hans-Georg Kräusslich. Analysis of the Diversity of the HIV-1 pol Gene and Drug Resistance Associated Changes among Drug-Naïve Patients in Burkina Faso. J. Med. Virol., 81(10):1691-701, Oct 2009. PubMed ID: 19697403. Show all entries for this paper.

Displaying record number 54087

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Species (MHC/HLA)	human(B*07)
Immunogen
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes this is a B*07 epitope.

References

Llano2019 Anuska Llano, Samandhy Cedeño, Sandra Silva Arrieta, and Christian Brander. The 2019 Optimal HIV CTL Epitopes Update: Growing Diversity in Epitope Length and HLA restriction. 2019. Show all entries for this paper.

Displaying record number 54181

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(156-164)
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	HLA associated polymorphism

Notes

Publicly available HIV-1 subtype C sequences from South Africa and Botswana were analyzed, and 94 HLA-associated amino acid polymorphisms were found. Many polymorphisms were associated with multiple HLA allele classes. 12% associations were negative: association of virus expression of the consensus amino acid with a specific HLA allele. HLA-B alleles accounted for 50% of associations. 19 HLA-associated polymorphisms were embedded in previously defined epitopes.
SPAIFQSSM was a previously defined B*07 presented epitope that encompassed a B*0702-associated polymorphism, SPAIFQsSM,in the seventh position.

References

Boutwell2007 Christian L. Boutwell and M. Essex. Identification of HLA Class I-Associated Amino Acid Polymorphisms in the HIV-1C Proteome. AIDS Res. Hum. Retroviruses, 23(1):165-174, Jan 2007. PubMed ID: 17263647. Show all entries for this paper.

Displaying record number 55346

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(156-164)
Epitope	`SPAIFQSSM`	Epitope Alignment
		Show epitope variants
Epitope Name	SM9
Subtype	B
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	epitope processing, computational epitope prediction, escape

Notes

E169D is a processing mutation for HLA-B*0702 restricted SPAIFQSSM (SM9) as well as an epitope variation for HLA-A*0301 restricted MTKILEPFR (MR9).
CTL recognition of SM9 was detected 5 days post-infection with wild type (169E) HIV-1, but not with mutant 169D virus.
Mutation 169D is 5 residues downstream of SM9. In vitro proteasome processing assays showed that the 27mer synthetic peptide QGWKGSPAIFQSSMTKILEPFRKQNPD released intermediate peptide QGWKGSPAIFQSSM within 6 h. Mutant peptide QGWKGSPAIFQSSMTKILdPFRKQNPD did not release this SM9-appropriate intermediate.

References

Zimbwa2007 Peter Zimbwa, Anita Milicic, John Frater, Thomas J. Scriba, Antony Willis, Philip J. R. Goulder, Tilly Pillay, Huldrych Gunthard, Jonathan N. Weber, Hua-Tang Zhang, and Rodney E. Phillips. Precise Identification of a Human Immunodeficiency Virus Type 1 Antigen Processing Mutant. J. Virol., 81(4):2031-2038, Feb 2007. PubMed ID: 17108020. Show all entries for this paper.

Displaying record number 61179

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
		Show epitope variants
Epitope Name	SM9
Subtype	B
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	acute/early infection, variant cross-reactivity

Notes

An 11-member cohort of acutely infected patients was studied to find that CTL cross-recognition of variant epitopes during acute infection is absent or poor as opposed to during chronic HIV-infection.
Pol epitope SPAIFQSSM, SM9_311-319,-specific T cells were less cytotoxic to variants than autologous SM9 in acute infection. No variants tested cross-reacted with T cells specific to autologous SM9.

References

Du2016 Victor Y. Du, Anju Bansal, Jonathan Carlson, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Kristin Ladell, Stephanie Gras, Tracy M. Josephs, Sonya L. Heath, David A. Price, Jamie Rossjohn, Eric Hunter, and Paul A. Goepfert. HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection. J. Immunol., 196(8):3276-3286, 15 Apr 2016. PubMed ID: 26983786. Show all entries for this paper.

Displaying record number 61858

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Subtype	B
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection, vaccine
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	vaccine-induced immune responses

Notes

The candidate tHIVconsvX vaccine is composed of 6 conserved Gag and Pol regions. Specific T cells - from 200 ART-naive, infected Japanese subjects previously exposed to the tHIVconsvX vaccine - that have the ability to supress HIV-1 replication were identified as recognizing 6 Pol epitopes. 6/25 epitopes (comprising 20 known and 5 novel mapped epitopes) remain associated with positive clinical outcome.
B*0702-restricted Pol epitope SPAIFQSSM was found in 15-mer peptide pairs C246/247. While 4/221 Japanese subjects responded to the epitope, only 2/20 HLA-carrying tested responders reacted to this epitope in EliSpot. SM9-specific CTL can strongly suppress HIV-1 replication in vivo. CTL response to B*0702-restricted SM9 is significantly associated with low pVL and found in B*0702-carrying subjects.

References

Zou2019 Chengcheng Zou, Hayato Murakoshi, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke, and Masafumi Takiguchi. Effective Suppression of HIV-1 Replication by Cytotoxic T Lymphocytes Specific for Pol Epitopes in Conserved Mosaic Vaccine Immunogens. J. Virol., 93(7), 1 Apr 2019. PubMed ID: 30674626. Show all entries for this paper.

Displaying record number 56490

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA associated polymorphism

Notes

HLA-associated polymorphisms were studied in a cohort of 710 chronic subtype C patients from South Africa. 84 HLA Class I-associated polymorphisms were identified, 73% of them with HLA-B. The viral set points associated with HLA allele correlated with the number of reversions associated with that allele, (HLA-B in Gag, HLA-C in Pol).
SPAIFQSSM is a previously described HLA-B*0702-restricted epitope (part of Pol(RT) reacting peptide GWKGSPAIFQsSMTKILEPFR) that contains a B*0702-associated sequence polymorphism at residue S (SPAIFQsSM).

References

Matthews2008 Philippa C. Matthews, Andrew Prendergast, Alasdair Leslie, Hayley Crawford, Rebecca Payne, Christine Rousseau, Morgane Rolland, Isobella Honeyborne, Jonathan Carlson, Carl Kadie, Christian Brander, Karen Bishop, Nonkululeko Mlotshwa, James I. Mullins, Hoosen Coovadia, Thumbi Ndung'u, Bruce D. Walker, David Heckerman, and Philip J. R. Goulder. Central Role of Reverting Mutations in HLA Associations with Human Immunodeficiency Virus Set Point. J. Virol., 82(17):8548-8559, Sep 2008. PubMed ID: 18596105. Show all entries for this paper.

Displaying record number 59049

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9-RT
Subtype	B, C
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	Japan, South Africa, United Kingdom, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	binding affinity, subtype comparisons

Notes

HLA-B*0702 is associated with rapid progression to disease in B-clade HIV-1 infected subjects. B*0702+ C-clade infected subjects however are not associated with a high viral setpoint of infection, and target a broader range of Gag epitopes at higher magnitudes. Increased magnitudes of Nef-specific responses were also detected in C-clade infected B*0702+ cohorts. A C-clade specific, B*0702-restricted novel p17 epitope, RPGGKKHYM, RM9, was defined.
Epitope SM9, SPAIFQSSM, a B- and C-clade RT epitope was targeted more by C-clade infected subjects than by B-clade infected individuals. The B-clade and C-clade consensus epitope is the same. Binding affinity of SM9 to B*0702 was K<sub>d</sub> = 37 nM. SM9 is contained within OLP187, QGWKGSPAIFQSSMTKIL.

References

Kloverpris2014 Henrik N. Kløverpris, Emily Adland, Madoka Koyanagi, Anette Stryhn, Mikkel Harndahl, Philippa C. Matthews, Roger Shapiro, Bruce D. Walker, Thumbi Ndung'u, Christian Brander, Masafumi Takiguchi, Søren Buus, and Philip Goulder. HIV Subtype Influences HLA-B*07:02-Associated HIV Disease Outcome. AIDS Res. Hum. Retroviruses, 30(5):468-475, May 2014. PubMed ID: 24010680. Show all entries for this paper.

Displaying record number 57995

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	computational epitope prediction, optimal epitope

Notes

A prediction tool, HLArestrictor, was developed to predict minimal epitopes from longer peptides. Minimal epitopes were predicted and validated for 18 EliSpot-positive 18mers.
SPAIFQSSM was predicted from EliSpot-positive 18mer QGWKGSPAIFQSSMTKIL. The epitope was validated in one B*0702-positive HIV-positive individual by tetramer staining.

References

ErupLarsen2011 Malene Erup Larsen, Henrik Kloverpris, Anette Stryhn, Catherine K. Koofhethile, Stuart Sims, Thumbi Ndung'u, Philip Goulder, Søren Buus, and Morten Nielsen. HLArestrictor---A Tool for Patient-Specific Predictions of HLA Restriction Elements and Optimal Epitopes within Peptides. Immunogenetics, 63(1):43-55, Jan 2011. PubMed ID: 21079948. Show all entries for this paper.

Displaying record number 61958

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Subtype	A3 (CRF02_AG+C), B
Species (MHC/HLA)	human(B0702, B3501)
Immunogen	HIV-1 infection
Patient MHC/HLA	1127: A0202, A3002, B0705, B1801; 1214: A0201, A3402, B4403, B8201; 1224: A3001, B1503, B*4201
Country	Denmark, Guinea-Bissau
Experimental methods	HLA binding, Intracellular cytokine staining, Tetramer binding
Keywords	binding affinity, vaccine antigen design

Notes

95% and 100% of untreated, asymptomatic HIV-1-infected patients, from Guinea-Bissau and Denmark respectively, were able to subdominantly recognize 15 predicted CTL epitopes restricted by at least one of the 5 most common HLA supertypes, HLA-A*01, -A*02, -A*03, -B*07 and -B*44.
Epitope SM9, SPAIFQSSM, predicted and validated to be restricted by supertype B07, was found across geographic regions in 94% of HIV-1 sequences in Denmark clade-B and 49% Guinea-Bissau/Western Africa subtype A3, the circulating recombinant form of clades C and CRF02_AG. Its equivalent peptide, Pol311 was able to elicit cytokine production and bound the following HLA alleles moderately or well: B*0702, B*3501 (B07 supertype).

References

Karlsson2012 Ingrid Karlsson, Henrik Kløverpris, Kristoffer Jarlov Jensen, Anette Stryhn, Søren Buus, Annika Karlsson, Lasse Vinner, Philip Goulder, and Anders Fomsgaard. Identification of Conserved Subdominant HIV Type 1 CD8+ T Cell Epitopes Restricted within Common HLA Supertypes for Therapeutic HIV Type 1 Vaccines. AIDS Res. Hum. Retroviruses, 28(11):1434-1443, Nov 2012. PubMed ID: 22747336. Show all entries for this paper.

Displaying record number 53312

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	( C consensus)
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B0702, B8101)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA cross-presentation, characterizing CD8+ T cells

Notes

HLA class I restricted CD8+ T-cell responses against HIV-1 were analyzed in African patients. Significantly more responses were shown to be HLA-B restricted. Viral load, CD4 count, and thus rate of disease progression were also associated with HLA-B alleles. In addition, the selection pressure imposed on HIV-1 by HLA-B alleles was shown to be substantially greater than by other alleles.
This epitope was suggested to be the epitope within a longer reactive peptide based on correspondence with a known epitope in the HIV database. Also, a significantly higher frequency of people in the Durban cohort who reacted with the peptide had this HLA type.

References

Kiepiela2004 Photini Kiepiela, Alasdair J. Leslie, Isobella Honeyborne, Danni Ramduth, Christina Thobakgale, Senica Chetty, Prinisha Rathnavalu, Corey Moore, Katja J. Pfafferott, Louise Hilton, Peter Zimbwa, Sarah Moore, Todd Allen, Christian Brander, Marylyn M. Addo, Marcus Altfeld, Ian James, Simon Mallal, Michael Bunce, Linda D. Barber, James Szinger, Cheryl Day, Paul Klenerman, James Mullins, Bette Korber, Hoosen M. Coovadia, Bruce D. Walker, and Philip J. R. Goulder. Dominant Influence of HLA-B in Mediating the Potential Co-Evolution of HIV and HLA. Nature, 432(7018):769-775, 9 Dec 2004. LA-UR 04-5920. PubMed ID: 15592417. Show all entries for this paper.

Displaying record number 60276

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Species (MHC/HLA)	human(B*1517)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
SPAIFQSSM had a significantly positive association with HLA B*1517; it was recognized by 1/1 B*1517-positive subjects and 4/231 B*1517-negative subjects.

References

Displaying record number 53113

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Species (MHC/HLA)	human(B*35)
Immunogen	HIV-1 infection
Country	Spain
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Proliferation
Keywords	HAART, ART, supervised treatment interruptions (STI)

Notes

Structured treatment interruption (STI) alone is not able to control viral replication in chronically infected patients, probably due to lack of strong, maintained T-helper cell responses. HIV-1 specific CD8+ T-cell responses were shown to increase significantly until the end of the follow up, but were not correlated with viral load.
5/9 patients recognized this epitope.

References

Plana2004 Montserrat Plana, Felipe Garcia, Annette Oxenius, Gabriel M. Ortiz, Anna Lopez, Anna Cruceta, Gabriel Mestre, Emilio Fumero, Catherine Fagard, Maria Antonia Sambeat, Ferran Segura, José M. Miró, Mireia Arnedo, L. Lopalcos, Tomas Pumarola, Bernard Hirschel, Rodney E. Phillips, Douglas F. Nixon, Teresa Gallart, and Jose M. Gatell. Relevance of HIV-1-Specific CD4+ Helper T-Cell Responses During Structured Treatment Interruptions in Patients With CD4+ T-Cell Nadir Above 400/mm3. J. Acquir. Immune Defic. Syndr., 36(3):791-799, 1 Jul 2004. PubMed ID: 15213562. Show all entries for this paper.

Displaying record number 440

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(311-319 SF2)
Epitope	`SPAIFQSSM`	Epitope Alignment
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review

Notes

Binds HLA-B*3501.
<cite>Menendez-Arias1998</cite>, in a review, notes that this epitope includes catalytic residues in the active site of RT.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Shiga1996 H. Shiga, T. Shioda, H. Tomiyama, Y. Takamiya, S. Oka, S. Kimura, Y. Yamaguchi, T. Gojoubori, H. G. Rammensee, K. Miwa, and M. Takiguchi. Identification of Multiple HIV-1 Cytotoxic T Cell Epitopes Presented by Human Leukocyte Antigen B35 Molecule. AIDS, 10:1075-1083, 1996. PubMed ID: 8874623. Show all entries for this paper.

Displaying record number 1424

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

One of the 51 HIV-1 epitopes selected by Ferrari et al. as good candidate CTL epitopes for vaccines by virtue of being conserved and presented by common HLA alleles.

References

Ferrari2000 G. Ferrari, D. D. Kostyu, J. Cox, D. V. Dawson, J. Flores, K. J. Weinhold, and S. Osmanov. Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines. AIDS Res. Hum. Retroviruses, 16(14):1433-43, 20 Sep 2000. PubMed ID: 11018863. Show all entries for this paper.

Displaying record number 441

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(311-319 SF2)
Epitope	`SPAIFQSSM`	Epitope Alignment
Species (MHC/HLA)	human(B*3501)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review

Notes

A CTL clone responsive to this epitope was obtained.
Only 1/7 B35-positive individuals had a CTL response to this epitope.
<cite>Menendez-Arias1998</cite>, in a review, notes that this epitope is near the active site of RT.

References

Tomiyama1997 H. Tomiyama, K. Miwa, H. Shiga, Y. I. Moore, S. Oka, A. Iwamoto, Y. Kaneko, and M. Takiguchi. Evidence of Presentation of Multiple HIV-1 Cytotoxic T Lymphocyte Epitopes by HLA-B*3501 Molecules That Are Associated with the Accelerated Progression of AIDS. J. Immunol., 158:5026-5034, 1997. PubMed ID: 9144523. Show all entries for this paper.

Displaying record number 60275

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Species (MHC/HLA)	human(B*39)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
SPAIFQSSM had a significantly positive association with HLA B*39; it was recognized by 4/25 B*39-positive subjects and 10/278 B*39-negative subjects.

References

Displaying record number 59451

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	RT-SM9
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	immunodominance, optimal epitope

Notes

2,093 HLA-B*4201⁺ ART-naive female adults from 5 cohorts with chronic C-clade infection were studied to determine factors controlling immunodominance. Immunodominant hierarchy of response observed across 20 HLA-B*4201-restricted epitopes was not linked to peptide-B*4201 binding affinity or stability. Immunodominance correlated instead with the particular amino acid residues within (TCRβ) TRB sequences. Extreme TCR biases towards generating identical or 'public' epitope-specific TCRs in multiple individuals therefore were statistically the greatest influence upon Immunodomination.
13 B*4201⁺-restricted novel epitopes were identified by EliSpot screening of 181 females with 410 HIV-1 OLPs.
11 different public clonotypes were identified and were used by the top 3 ranked immunodominant epitope-specificities.
6/10 most immunodominant epitopes were Gag/Pol/Vpr-specific and 100% showed selection pressure on HIV. Of 4 epitopes that were Nef/Vif-specific and among most immunodominant, only 25% i.e one epitope experienced selection pressure in the virus.
Optimal epitope SPAIFQSSM from OLP RT-187 (QGWKGSPAIFQSSMTKIL) had a targeting frequency of ˜3% of 154 HLA-B*4201⁺ subjects. Immunodominance rank was 17/20 tested epitopes.
RT-SM9-HLA-B*4202's binding affinity, K_d = 3 nM; stability, K_1/2 = 12h.

References

Kloverpris2015 Henrik N Kløverpris, Reuben McGregor, James E. McLaren, Kristin Ladell, Mikkel Harndahl, Anette Stryhn, Jonathan M. Carlson, Catherine Koofhethile, Bram Gerritsen, Can Keşmir, Fabian Chen, Lynn Riddell, Graz Luzzi, Alasdair Leslie, Bruce D. Walker, Thumbi Ndung'u, Søren Buus, David A. Price, and Philip J. Goulder. CD8+ TCR Bias and Immunodominance in HIV-1 Infection. J. Immunol., 194(11):5329-5345, 1 Jun 2015. PubMed ID: 25911754. Show all entries for this paper.

Displaying record number 58721

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(146-154)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	RT-SM9
Subtype	C
Species (MHC/HLA)	human(B*4202)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3001, B4202, Cw*1701
Country	Botswana, South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA associated polymorphism, novel epitope

Notes

Using an outbred cohort of 2,093 clade-C-infected southern African subjects who carry the HLA-B*42 allele, the authors determine that a single amino acid change between B*4202 and B*4201 is responsible for the difference in HLA-B*4201 presenting multiple Gag epitopes with a lower VL; and HLA-B*0402 which presents no p24 Gag epitopes. Thus a single nucleotide polymorphism (SNP) on the HLA class I locus is associated with significant differences in HIV disease control.
While no substantial difference was seen in the peptide binding motifs of both HLAs, as well as no overall difference in targeting of Pol, Nef or Env epitopes, a significantly larger number of HLA-B*4201-positive subjects recognized Gag epitopes.
RT epitope SM9, SPAIFQSSM, was recognized by ∼60% B*4202-positive responding subjects versus ∼20% of HLA-B*4201 carriers. It is a novel C-clade epitope restricted by HLA-B*4202.

References

Kloverpris2012a Henrik N. Kløverpris, Mikkel Harndahl, Alasdair J. Leslie, Jonathan M. Carlson, Nasreen Ismail, Mary van der Stok, Kuan-Hsiang Gary Huang, Fabian Chen, Lynn Riddell, Dewald Steyn, Dominique Goedhals, Cloete van Vuuren, John Frater, Bruce D. Walker, Mary Carrington, Thumbi Ndung'u, Søren Buus, and Philip Goulder. HIV Control through a Single Nucleotide on the HLA-B Locus. J. Virol., 86(21):11493-11500, Nov 2012. PubMed ID: 22896606. Show all entries for this paper.

Displaying record number 54000

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	( C consensus)
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*4202)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
SPAIFQSSM is an optimal epitope.

References

Kiepiela2007 Photini Kiepiela, Kholiswa Ngumbela, Christina Thobakgale, Dhanwanthie Ramduth, Isobella Honeyborne, Eshia Moodley, Shabashini Reddy, Chantal de Pierres, Zenele Mncube, Nompumelelo Mkhwanazi, Karen Bishop, Mary van der Stok, Kriebashnie Nair, Nasreen Khan, Hayley Crawford, Rebecca Payne, Alasdair Leslie, Julia Prado, Andrew Prendergast, John Frater, Noel McCarthy, Christian Brander, Gerald H. Learn, David Nickle, Christine Rousseau, Hoosen Coovadia, James I. Mullins, David Heckerman, Bruce D. Walker, and Philip Goulder. CD8+ T-Cell Responses to Different HIV Proteins Have Discordant Associations with Viral Load. Nat. Med., 13(1):46-53, Jan 2007. PubMed ID: 17173051. Show all entries for this paper.

Displaying record number 58722

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(146-154)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	RT-SM9
Subtype	C
Species (MHC/HLA)	human(B*4202)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3001, B4202, Cw*1701
Country	Botswana, South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA associated polymorphism, novel epitope

Notes

Using an outbred cohort of 2,093 clade-C-infected southern African subjects who carry the HLA-B*42 allele, the authors determine that a single amino acid change between B*4202 and B*4201 is responsible for the difference in HLA-B*4201 presenting multiple Gag epitopes with a lower VL; and HLA-B*0402 which presents no p24 Gag epitopes. Thus a single nucleotide polymorphism (SNP) on the HLA class I locus is associated with significant differences in HIV disease control.
While no substantial difference was seen in the peptide binding motifs of both HLAs, as well as no overall difference in targeting of Pol, Nef or Env epitopes, a significantly larger number of HLA-B*4201-positive subjects recognized Gag epitopes.
RT epitope SM9, SPAIFQSSM, was recognized by ˜60% B*4202-positive responding subjects versus ˜20% of HLA-B*4201 carriers. It is a novel C-clade epitope restricted by HLA-B*4202.

References

Displaying record number 54296

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	B7-SM9(RT)
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, immunodominance, early-expressed proteins

Notes

Immunodominant HIV epitopes in early, primary infection of CTLs were identified and the relative contribution of immune responses restricted to individual HLA class I molecules were studied.
The most frequently recognised epitopes also elicited the greatest CTL response.
HIV-1 Epitope sequence variability was not correlated with immunodominant versus immune sub-dominant responses.
HLA-B*57 and HLA-B*27 restricted responses were the strongest in these early and acute infections - due to dominant responses to a single epitope in each case (TW10 for B*57 and KK10 for B*27).
In the presence of HLA-B*57 and HLA-B*27 restricted responses, the relative contribution of other restricting HLA dropped greatly.

References

Altfeld2006 Marcus Altfeld, Elizabeth T. Kalife, Ying Qi, Hendrik Streeck, Mathias Lichterfeld, Mary N. Johnston, Nicole Burgett, Martha E. Swartz, Amy Yang, Galit Alter, Xu G. Yu, Angela Meier, Juergen K. Rockstroh, Todd M. Allen, Heiko Jessen, Eric S. Rosenberg, Mary Carrington, and Bruce D. Walker. HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1. PLoS Med., 3(10):e403, Oct 2006. PubMed ID: 17076553. Show all entries for this paper.

Displaying record number 1547

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(323-331 SF2)
Epitope	`SPAIFQSSM`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, acute/early infection

Notes

Therapy provided during acute infection resulted in a narrower CTL response, stronger T help response, and a less diverse viral population than was seen in individuals treated during chronic infection.
The breadth and specificity of the response was determined using ELISPOT by studying 19 individuals with pre-seroconversion therapy (Group 1), 11 individuals with primary infection but post-seroconversion therapy (Group 2), and 10 individuals who responded to HAART given during chronic infection (Group 3), using 259 overlapping peptides spanning p17, p24, RT, gp41, gp120 and Nef.
Previously described and newly defined optimal epitopes were tested for CTL response.
Number of HLA-B7+ individuals that had a CTL response to this epitope broken down by group: 0/4 group 1, 0/3 group 2, and 1/1 group 3.

References

Altfeld2001b M. Altfeld, E. S. Rosenberg, R. Shankarappa, J. S. Mukherjee, F. M. Hecht, R. L. Eldridge, M. M. Addo, S. H. Poon, M. N. Phillips, G. K. Robbins, P. E. Sax, S. Boswell, J. O. Kahn, C. Brander, P. J. Goulder, J. A. Levy, J. I. Mullins, and B. D. Walker. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J. Exp. Med., 193(2):169-80, 15 Jan 2001. URL: http://www.jem.org/cgi/content/full/193/2/169. PubMed ID: 11148221. Show all entries for this paper.

Displaying record number 1493

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol
Epitope	`SPAIFQSSM`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, acute/early infection

Notes

Subject 053i was followed longitudinally from acute infection through death, and had rapid progression to AIDS.
This individual had a dominant response to IPRRIRQGL with strong in vivo activated responses and in vitro stimulated memory responses and a subdominant response to SPAIFQSSM -- during the course of disease progression (4 Years), the functional CTL responses were lost and no sequence variation occurred with in both epitopes, but CTL clones specific for IPRRIRQGL persisted throughout.

References

Islam2001 S. A. Islam, C. M. Hay, K. E. Hartman, S. He, A. K. Shea, A. K. Trocha, M. J. Dynan, N. Reshamwala, S. P. Buchbinder, N. O. Basgoz, and S. A. Kalams. Persistence of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte clones in a subject with rapid disease progression. J. Virol., 75(10):4907-11, May 2001. URL: http://jvi.asm.org/cgi/content/full/75/10/4907. PubMed ID: 11312363. Show all entries for this paper.

Displaying record number 61008

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(156-164)
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	44149: A0101, A2401, B0701, B0801, Cw0701, Cw0702; 63794: A0201, A0201, B0701, B4401, Cw0702, Cw0704
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The extent to which set-point viremia is affected by early HIV-infection T cell responses to either conserved or variable epitopes was studied. 23 ART-naive subjects were characterized for CTL responses for 6 months, postinfection. While most CTL responses (73/123) were targeted against variable HIV-1 epitopes, recognition of conserved epitopes (16/123) was associated with lower set point viremia. This was independent of HLA type and also functional avidity of the CTL response. Most of the conserved responses were targeted to Gag and Pol epitopes.
SPAIFQSSM, restricted by B7, was recognized by 2 patients with the restricting allele.

References

Kunwar2013 Pratima Kunwar, Natalie Hawkins, Warren L. Dinges, Yi Liu, Erin E. Gabriel, David A. Swan, Claire E. Stevens, Janine Maenza, Ann C. Collier, James I. Mullins, Tomer Hertz, Xuesong Yu, and Helen Horton. Superior Control of HIV-1 Replication by CD8+ T Cells Targeting Conserved Epitopes: Implications for HIV Vaccine Design. PLoS One, 8(5):e64405, 2013. PubMed ID: 23741326. Show all entries for this paper.

Displaying record number 442

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(156-164 HXB2)
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, immunodominance

Notes

CTL response to IPRRIRQGL was the immunodominant response in a rapid progressor -- there was a subdominant response to SPAIFQSSM in Pol, and interestingly, no response to commonly immunodominant HLA A*0201 epitope SLYNTVATL, although this individual was HLA A*0201.
The individual showed a strong initial CTL response at the time of the initial drop in viremia, but it was quickly lost, although memory cells persisted.
Despite the initial narrow response to two epitopes, no other CTL responses developed.
No HIV-specific lymphoproliferative responses were detected in this patient, and neutralizing antibody response was weak.
Variants of this epitopes were observed in vivo (spaifqCsm, spSifqssm), but the binding motifs for B7 were preserved (P2, and C-term aromatic or hydrophobic)

References

Hay1999a C. Hay, D. Ruhl, N. Basgoz, C. Wilson, J. Billingsley, M. DePasquale, R. D'Aquila, S. M. Wolinsky, J. M Crawfod, D. Montefiori, and B. D. Walker. Lack of Viral Escape and Defective In Vivo Activation of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes in Rapidly Progressive Infection. J. Virol., 73:5509-5519, 1999. PubMed ID: 10364299. Show all entries for this paper.

Displaying record number 53551

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(312-320)
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A3, B57, B7, Cw6, Cw7
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords

Notes

Two-thirds of all mutations arising in non-envelope proteins during the transition from acute to chronic infection were found to be due to either CD8 T-cell-associated selective pressures or reversion of HLA-I-associated mutations selected in a previous host.The predominance of escape mutations at highly polymorphic sites was observed across different HIV-1 clades.
This epitope was reactive, but escape mutations did not accrue in it over time.

References

Allen2005a Todd M. Allen, Marcus Altfeld, Shaun C. Geer, Elizabeth T. Kalife, Corey Moore, Kristin M. O'Sullivan, Ivna DeSouza, Margaret E. Feeney, Robert L. Eldridge, Erica L. Maier, Daniel E. Kaufmann, Matthew P. Lahaie, Laura Reyor, Giancarlo Tanzi, Mary N. Johnston, Christian Brander, Rika Draenert, Jurgen K. Rockstroh, Heiko Jessen, Eric S. Rosenberg, Simon A. Mallal, and Bruce D. Walker. Selective Escape from CD8+ T-Cell Responses Represents a Major Driving Force of Human Immunodeficiency Virus Type 1 (HIV-1) Sequence Diversity and Reveals Constraints on HIV-1 Evolution. J. Virol., 79(21):13239-13249, Nov 2005. PubMed ID: 16227247. Show all entries for this paper.

Displaying record number 53498

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, escape, characterizing CD8+ T cells, viral fitness and reversion

Notes

Two-thirds of all mutations arising in non-envelope proteins during the transition from acute to chronic infection were found to be due to either CD8 T-cell-associated selective pressures or reversion of HLA-I-associated mutations selected in a previous host.The predominance of escape mutations at highly polymorphic sites was observed across different HIV-1 clades.
One escape mutation, at position 7, spaifqCsm, was found in the most polymorphic residue in the epitope. This was shared between clades B and C.

References

Displaying record number 53368

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	( B consensus)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, B7, Cw7
Experimental methods	Chromium-release assay, Cytokine production, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	assay or method development, memory cells, characterizing CD8+ T cells

Notes

Using a flow-cytometric cytotoxicity assay based on caspase-3 activation in dying target cells, it was shown that the subset of HIV-1-specific CD8+ T cells secreting both IFN-gamma and TNF-alpha exhibit stronger cytotoxic activity than those secreting only IFN-gamma. These cells also exhibited stronger intracellular perforin expression. No association between HIV-1-specific CD8+ T-cell maturation phenotypes and intracellular perforin expression was found.
1/9 individuals recognized this epitope.

References

Lichterfeld2004b Mathias Lichterfeld, Xu G. Yu, Michael T. Waring, Stanley K. Mui, Mary N. Johnston, Daniel Cohen, Marylyn M. Addo, John Zaunders, Galit Alter, Eunice Pae, Daryld Strick, Todd M. Allen, Eric S. Rosenberg, Bruce D. Walker, and Marcus Altfeld. HIV-1-Specific Cytotoxicity Is Preferentially Mediated by a Subset of CD8+ T Cells Producing both Interferon-gamma and Tumor Necrosis Factor-alpha. Blood, 104(2):487-394, 15 Jul 2004. PubMed ID: 15059848. Show all entries for this paper.

Displaying record number 58419

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	Pol311
Subtype	B, CRF02_AG
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	Cote D'Ivoire, Denmark, Ghana, Guinea-Bissau, Mali, Senegal
Experimental methods	Intracellular cytokine staining, Pentamer labeling
Keywords	vaccine antigen design

Notes

15 subdominant CTL epitopes were used to study 2 new Guinea-Bissau HIV-1 isolates, a newly completed Danish subtype B genome sequence and other previously published West African sequences. Subtype analysis showed the 2 new Guinea-Bissau sequences were CRF02_AG inter-subtype recombinant forms with typical cross-over points. The 15 epitopes were restricted by common HLA alleles (A1, A2, A3, B7, B44) and were present and conserved in all sequences studied. Mean conservation of the epitopes in local strains was 76% and 70% for Denmark and West Africa respectively. All epitopes had been previously confirmed as antigenic [Perez2008].
Pol311 epitope, SPAIFQSSM, showed a conservation of amino acid identity of 94% for the Danish sequence and 49% for the West African sequences.

References

Perez2008 Carina L. Pérez, Mette V. Larsen, Rasmus Gustafsson, Melissa M. Norström, Ann Atlas, Douglas F. Nixon, Morten Nielsen, Ole Lund, and Annika C. Karlsson. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes. J. Immunol., 180(7):5092-5100, 1 Apr 2008. PubMed ID: 18354235. Show all entries for this paper.

Vinner2011 Lasse Vinner, Birgitta Holmgren, Kristoffer J. Jensen, Joakim Esbjornsson, Marie Borggren, Julie L. Hentze, Ingrid Karlsson, Betina S. Andresen, Gregers J. Gram, Henrik Kloverpris, Peter Aaby, Zacarias José Da Silva, Eva-Maria Fenyö, and Anders Fomsgaard. Sequence Analysis of HIV-1 Isolates from Guinea-Bissau: Selection of Vaccine Epitopes Relevant in Both West African and European Countries. APMIS, 119(8):487-497, Aug 2011. PubMed ID: 21749448. Show all entries for this paper.

Displaying record number 58677

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location
Epitope	`SPAIFQSSM`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supertype, HLA cross-presentation, optimal epitope

Notes

100 HIV-infected subjects were tested for response to optimally-defined CTL epitopes regardless of the subject's HLA type. Half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Statistical and experimental methods were used to define additional HLA alleles associated with the epitopes.
In addition to its known HLA association (B07), 2 additional HLAs (B42, B81) were statistically predicted to be associated with this optimal epitope, SPAIFQSSM.

References

Frahm2007b Nicole Frahm, Karina Yusim, Todd J. Suscovich, Sharon Adams, John Sidney, Peter Hraber, Hannah S. Hewitt, Caitlyn H. Linde, Daniel G. Kavanagh, Tonia Woodberry, Leah M. Henry, Kellie Faircloth, Jennifer Listgarten, Carl Kadie, Nebojsa Jojic, Kaori Sango, Nancy V. Brown, Eunice Pae, M. Tauheed Zaman, Florian Bihl, Ashok Khatri, Mina John, Simon Mallal, Francesco M. Marincola, Bruce D . Walker, Alessandro Sette, David Heckerman, Bette T. Korber, and Christian Brander. Extensive HLA Class I Allele Promiscuity among Viral CTL Epitopes. Eur. J. Immunol., 37(9):2419-2433, Sep 2007. PubMed ID: 17705138. Show all entries for this paper.

Displaying record number 52914

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location
Epitope	`SPAIFQSSM`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	epitope processing, assay or method development

Notes

96% of optimally defined epitopes have one of only nine amino acids serving as the C-terminal anchor position. Seven amino acids are never found in this position and four are only present in 4% of cases. CD8 T-cell response to an epitope is shown to be best detected when the epitope is situated at the C-terminal end of a longer peptide, and authors suggest that Elispot reagents would be better designed if peptides ended on known C-terminal anchors.
SPAIFQSSM is suggested to be the optimal epitope instead of SPAIFQSSMT.

References

Draenert2004 Rika Draenert, Christian Brander, Xu G. Yu, Marcus Altfeld, Cori L. Verrill, Margeret E. Feeney, Bruce D. Walker, and Philip J. R. Goulder. Impact of Intrapeptide Epitope Location on CD8 T Cell Recognition: Implications for Design of Overlapping Peptide Panels. AIDS, 18(6):871-876, 9 Apr 2004. PubMed ID: 15060434. Show all entries for this paper.

Displaying record number 52820

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(156-164)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	B7-SM9 Pol
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supervised treatment interruptions (STI), escape, early treatment, superinfection

Notes

An HIV+ individual given acute ARV and undergoing STI developed a strong CTL immune response, but despite this was shown to be superinfected with second B clade virus. Some epitope variants of the second infecting virus were resistant to the initial CTL response; this epitope did not vary.

References

Altfeld2002a Marcus Altfeld, Todd M. Allen, Xu G. Yu, Mary N. Johnston, Deepak Agrawal, Bette T. Korber, David C. Montefiori, David H. O'Connor, Ben T. Davis, Paul K. Lee, Erica L. Maier, Jason Harlow, Philip J. R. Goulder, Christian Brander, Eric S. Rosenberg, and Bruce D. Walker. HIV-1 Superinfection Despite Broad CD8+ T-Cell Responses Containing Replication of the Primary Virus. Nature, 420(6914):434-439, 28 Nov 2002. PubMed ID: 12459786. Show all entries for this paper.

Displaying record number 52167

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(156-164)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	B7-SM9
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, B7, Cw7
Experimental methods
Keywords	dynamics, supervised treatment interruptions (STI), acute/early infection

Notes

CTL responses in 18 acutely HIV-infected HLA-A3 (n=7) or -B7 (n=4) or both -A3 and B7 (n=7) positive individuals were studied.
One individual, AC-06, was homozygous at all three class I alleles (A3, B7, Cw7), was treated during acute infection and had supervised treatment interruptions (STI). He had only two detectable CTL responses during acute infection, but after STI this broadened to 27 distinct epitopes including 15 restricted by HLA-A3, 11 by HLA-B7, and 1 by HLA-Cw7.
1/11 HLA-B7 individuals had detectable B7-restricted responses to this epitope during acute infection -- 10/15 of HLA-B7 epitopes tested were targeted by at least one person during acute infection. 3/4 individuals had detectable responses to this epitope after STI.

References

Yu2002b Xu G. Yu, Marylyn M. Addo, Eric S. Rosenberg, William R. Rodriguez, Paul K. Lee, Cecily A. Fitzpatrick, Mary N. Johnston, Daryld. Strick, Philip J. R. Goulder, Bruce D. Walker, and Marcus Altfeld. Consistent Patterns in the Development and Immunodominance of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T-Cell Responses Following Acute HIV-1 Infection. J. Virol., 76(17):8690-8701, Sep 2002. PubMed ID: 12163589. Show all entries for this paper.

Displaying record number 60273

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol(311-319)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Species (MHC/HLA)	human(C*08)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
SPAIFQSSM had a significantly positive association with HLA C*08; it was recognized by 3/33 C*08-positive subjects and 1/198 C*08-negative subjects.

References

Displaying record number 55480

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	A1, B, C, CRF01_AE, D
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction, variant cross-reactivity, vaccine antigen design

Notes

From HIV-1 sequences of multiple subtypes, bioinformatic prediction generated 174 CTL epitopes from Gag, Pol, Nef, Env and Tat restricted by HLA supertypes A1, A2, A3, A24, B7, B44 and B58; 10 previously-published A2- and B58-restricted epitopes were also included. Of these 184 epitopes, 113 were recognized experimentally in serum from 31 HIV+ patients.
While Gag, Pol, Env and Nef were highly immunogenic, only 38% of Tat epitopes elicited a response.
SPAIFQSSM was a predicted epitope restricted by B7 supertype. 7/31 patient(s) responded to it; 6 responding patients were known to carry an allele of B7 supertype. Responding patients were infected with HIV clade(s) A1, B, C, D, CRF01_AE.
One of 21 epitopes denoted as elite, having a response in 4 or more of the 31 patients.
Broadly immunogenic epitope SPAIFQSSM, had subtype variants that were recognized by less than half its patient responders. This epitope is predicted to be restricted by HLA supertype B7.

References

Displaying record number 54196

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT(156-164)
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	supertype, HLA cross-presentation, TCR usage, HLA associated polymorphism

Notes

14 promiscuous HIV-specific CTL epitopes presented by B7 supertype alleles were described. It was shown that CTLs targeting an identical epitope that are restricted by closely related but different HLA alelles differ in several ways: by occurrence of distinct HLA-specific escape mutations, by recruitment of distinct TCRs by peptide/MHC complexes, and by functional avidity of CTLs. Since there were no differences in the frequency, magnitude or immunodominance of the CTL responses restricted by different HLA alleles, it is suggested that the unique peptide/MHC complexes generated by closely related HLA induce qualitatively different CTL responses.
Functional avidity is correlated with selection pressure observed in HLA allele-epitope restriction
Statistically significant associations between numbers of HLA-0702 and -B8101 expressing subjects and epitope SPAIFQSSM were found.
Only B*0702 was found to be associated with polymorphism in SM9.

References

Leslie2006 Alasdair Leslie, David A. Price, Pamela Mkhize, Karen Bishop, Almas Rathod, Cheryl Day, Hayley Crawford, Isobella Honeyborne, Tedi E. Asher, Graz Luzzi, Anne Edwards, Christine M. Rousseau, James I. Mullins, Gareth Tudor-Williams, Vas Novelli, Christian Brander, Daniel C. Douek, Photini Kiepiela, Bruce D. Walker, and Philip J. R. Goulder. Differential Selection Pressure Exerted on HIV by CTL Targeting Identical Epitopes but Restricted by Distinct HLA Alleles from the Same HLA Supertype. J. Immunol., 177(7):4699-4708, 1 Oct 2006. PubMed ID: 16982909. Show all entries for this paper.

Displaying record number 58067

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	Pol
Epitope	`SPAIFQSSM`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5), DNA prime with Ad5 boost
Vaccine strain	B clade IIIB, B clade JRFL, B clade CAM-1
Vaccine component	Gag, Nef, Pol

Notes

T-cell epitope response specificities were examined in uninfected subjects who received the Gag/Pol/Nef vaccine used in the Step trial. Variable epitopes were detected more frequently than would be expected from an unbiased sampling. The most conserved epitopes were detected at a lower frequency, similar to the frequency reported for responses to natural infection, suggesting potential epitope masking. This may be a mechanism used by the virus in both contexts to escape effective T-cell surveillance. Development of vaccine strategies that can elicit a greater breadth, and towards conserved regions of the genome in particular, are critical requirements for effective T-cell based vaccines.
All vacinees had responses to the Gag peptide pool, and most also had responses to the Nef and/or Pol pools. Subsequent mapping using 9mer minipools demonstrated that T-cell epitopes were recognized across the length of all 3 proteins. A total of 105 distinct 9mers were detected, although some of these may have been overlapping 9mers representing a single epitope.
2 vaccinees recognized 9mer SPAIFQSSM.
Database note: this 9mer contains known epitope SPAIFQSS. The HLA restriction of this epitope in the database is B7, and both responding subjects carry a B7 allele.

References

Li2011a Fusheng Li, Adam C. Finnefrock, Sheri A. Dubey, Bette T. M. Korber, James Szinger, Suzanne Cole, M. Juliana McElrath, John W. Shiver, Danilo R. Casimiro, Lawrence Corey, and Steven G Self. Mapping HIV-1 Vaccine Induced T-Cell Responses: Bias Towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study. PLoS One, 6(6):e20479, 2011. PubMed ID: 21695251. Show all entries for this paper.

Displaying record number 57497

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT Pol(156-164)
Epitope	`SPAIFQSSM`	Epitope Alignment
		Show epitope variants
Epitope Name	SM9
Subtype	A1, B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Somalia, Uganda, United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	variant cross-reactivity

Notes

6 epitopes and their variants were tested for quantitative CTL recognition in a genetically diverse cohort of 26 HIV-1+ subjects from 12 countries, to determine response pattern as correlating to HLA genotype & autologous virus sequence. Cross-reactive epitopes were more similar, with a single substitution decreasing recognition by 40%. Central residues in an epitope were more important for recognition.
Epitope SM9, SPAIFQSSM, elicited CTL response in 3 patients - 2059 (Caucasian male, treated, autologous virus Clade B); 2632 (African female, experienced some treatment, autologous virus Clade A1); 3076 (African female, treatment naive, autologous virus Clade A1).

References

Hoof2010 Ilka Hoof, Carina L. Pérez, Marcus Buggert, Rasmus K. L. Gustafsson, Morten Nielsen, Ole Lund, and Annika C. Karlsson. Interdisciplinary Analysis of HIV-Specific CD8+ T Cell Responses against Variant Epitopes Reveals Restricted TCR Promiscuity. J Immunol, 184(9):5383-5391, 1 May 2010. PubMed ID: 20363973. Show all entries for this paper.

Displaying record number 55980

HXB2 Location	Pol(311-319) RT(156-164) DNA(3015..3041)	Pol Epitope Map
Author Location	RT
Epitope	`SPAIFQSSM`	Epitope Alignment
Epitope Name	SM9(RT)
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	non-susceptible form

Notes

49 ART-naive chronically HIV-1 infected Chinese subjects' CTLs were tested with 413 OLPs in IFN-gamma assays, determining optimal epitopes specific for Chinese Clade B HIV-1 sequences.
An inverse correlation was found between CTL response and viral load.
Targeted peptides have lower entropy than peptides that are not CTL targeted. This correlation is independent of HLA-restriction.
The tested peptide sequence, QGWKGSPAIFQCSMTKIL, contains a variant, SPAIFQcSM, that differs by 1 substitution from the previously described HLA-B7 epitope SPAIFQSSM. None of the 16 HLA-B7 carriers responded to a variant SPAIFQcSM.

References

Zhai2008 Song Zhai, Yan Zhuang, Yang Song, Shu Li, Dedong Huang, Wenzhen Kang, Xinhong Li, Qi Liao, Yanhou Liu, Zhongfang Zhao, Yichen Lu, and Yongtao Sun. HIV-1-Specific Cytotoxic T Lymphocyte (CTL) Responses Against Immunodominant Optimal Epitopes Slow the Progression of AIDS in China. Curr. HIV Res., 6(4):335-350, Jun 2008. PubMed ID: 18691032. Show all entries for this paper.