Search CTL/CD8+ T-Cell Epitope Database

Found 27 matching records:

Displaying record number 59770

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(216-224)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9
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.
HPVHAGPIA had a significantly positive association with HLA A*6802; it was recognized by 10/26 A*6802-positive subjects and 53/278 A*6802-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 59142

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	p24
Epitope	`HPVHAGPIA`	Epitope Alignment
		Show epitope variants
Epitope Name	HA9
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.
B*07-restricted p24 HA9, HPVHAGPIA, elicited no CTL response when tested by EliSpot. Patient autologous sequence was HPVHAGPvA.

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 52548

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	p24(84-92)
Epitope	`HPVHAGPIA`	Epitope Alignment
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope

Notes

An optimal epitope, based on data from Yu et al. 2002 [PMID 12163589] and Westrop et al. 2009 [PMID 19056394]. Restricted by B*07.

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 59043

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	p24
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9-p24
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 HA9, HPVHAGPIA, a B- and C-clade Gag epitope was targeted more by C-clade infected subjects than B-clade ones. The B-clade and C-clade consensus epitope is the same. Binding affinity of HA9 to B*0702 was Kd = 32 nM. HA9 is contained within OLP29, AAEWDRLHPVHAGPIA.

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 56202

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(237-)
Epitope	`HPVHAGPIA`	Epitope Alignment
Species (MHC/HLA)	human(B*0702)
Immunogen	vaccine
Country	Botswana, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine strain	multiple epitope immunogen

Notes

This is a trial of a multi-epitope DNA vaccine that included 21 CTL epitopes, which are conserved among clades A,B,C,D and CRFs and are supertype binding peptides of A1, A3 and B7 supertypes. Participants were from US and Botswana.
The vaccine was safe and well-tolerated, but the rate of CTL induction was low. CD8+ responses (and no CD4+ responses) were detected in 3/26 subjects using chromium release assay and in 2/42 subjects using IFN-γ ELISPOT assay.
This epitope was included in the vaccine.

References

Gorse2008a Geoffrey J. Gorse, Lindsey R. Baden, Margaret Wecker, Mark J. Newman, Guido Ferrari, Kent J. Weinhold, Brian D. Livingston, Tonya L. Villafana, Hongli Li, Elizabeth Noonan, Nina D. Russell, and HIV Vaccine Trials Network. Safety and Immunogenicity of Cytotoxic T-Lymphocyte Poly-Epitope, DNA Plasmid (EP HIV-1090) Vaccine in Healthy, Human Immunodeficiency Virus Type 1 (HIV-1)-Uninfected Adults. Vaccine, 26(2):215-223, 10 Jan 2008. PubMed ID: 18055072. Show all entries for this paper.

Displaying record number 53970

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`HPVHAGPIA`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B35)
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.
HPVHAGPIA 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 53296

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`HPVHAGPIA`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	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 55872

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag
Epitope	`HPVHAGPIA`	Epitope Alignment
Subtype	B, C, D
Species (MHC/HLA)	human(B35, B7)
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	subtype comparisons

Notes

By studying Gag p24 in different subtypes of subjects, previously discovered and new epitopes were identified. New T cell epitopes, both CD8 and CD4, related to the patients' HLA are described.
T cells cross-reacted to peptides from different patient subtypes, and this cross-reactivity was distributed along the entire p24 protein.
HLA-B7-restricted epitope HPVHAGPIA is from a subtype B peptide library, and is reactive as part of peptide EWDRVHPVHAGPIAP in a subtype B-carrying subject. HLA-B35-restricted epitope HPVHAGPIA is from a subtype C peptide library, and is reactive as part of peptide HPVHAGPIAPGQMRE in a subtype D-carrying subject.

References

Gudmundsdotter2008 L. Gudmundsdotter, D. Bernasconi, B. Hejdeman, E. Sandstrom, A. Alaeus, K. Lidman, B. Ensoli, B. Wahren, and S. Buttò. Cross-Clade Immune Responses to Gag p24 in Patients Infected with Different HIV-1 Subtypes and Correlation with HLA Class I and II Alleles. Vaccine, 26(40):5182-5187, 19 Sep 2008. PubMed ID: 18479789. Show all entries for this paper.

Displaying record number 61891

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(216-224)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9, p24HA9
Subtype	B
Species (MHC/HLA)	human(B*3501)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining, Tetramer binding
Keywords	escape, HLA associated polymorphism

Notes

HLA-B*3501 is known to be a detrimental allele associated with rapid progression to AIDS. CTL responses to 16 known HLA-B*3501-restricted epitopes however, were studied in 63 B*3501+ ART-naive Japanese subjects, to find B*3501-epitope-specific CTLs which can suppress HIV-1 replication. The effect of viral protective-epitope mutations associated with B*3501 were also investigated and so one mechanism of the detrimental effect of HLA-B*3501 was clarified: the Y135F mutation within NefYF9, which is selected by HLA-A*2402-restricted CTL, impairs the ability of YF9-specific CTL to suppress HIV replication both in vivo and in vitro.
Gag epitope HPVHAGPIA (HA9) elicited CTL response in 15/63 HLA-B*3501+ HIV-1-infected ART naive Japanese subjects, but no significant association was found with suppression of pVL (plasma viral load).

References

Murakoshi2018a Hayato Murakoshi, Madoka Koyanagi, Tomohiro Akahoshi, Takayuki Chikata, Nozomi Kuse, Hiroyuki Gatanaga, Sarah L. Rowland-Jones, Shinichi Oka, and Masafumi Takiguchi. Impact of a Single HLA-A*24:02-Associated Escape Mutation on the Detrimental Effect of HLA-B*35:01 in HIV-1 Control. EBioMedicine, 36:103-112, Oct 2018. PubMed ID: 30249546. Show all entries for this paper.

Displaying record number 57477

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(216-224)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9
Subtype	B
Species (MHC/HLA)	human(B*3501)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Cytokine production, Flow cytometric T-cell cytokine assay, HLA binding
Keywords	computational epitope prediction

Notes

44 candidate B*3501-restricted epitopes were predicted by computational analysis of HIV-1 Gag. Twelve candidates had significant binding affinity for HLA-B*3501. Two previously-unknown candidates also had positive EliSpot responses among 4 chronically-infected B35-positive patients carrying subtype B HIV-1.
Novel epitope HPVHAGPIA had significant binding affinity for HLA-B*3501 and a positive IFN-gamma EliSpot response in 4/4 HLA-B*3501-positive patients.

References

Westrop2009 Samantha J. Westrop, Nathali Grageda, and Nesrina Imami. Novel Approach to Recognition of Predicted HIV-1 Gag B3501-Restricted CD8 T-Cell Epitopes by HLA-B3501+ Patients: Confirmation by Quantitative ELISpot Analyses and Characterisation Using Multimers. J. Immunol. Methods, 341(1-2):76-85, 28 Feb 2009. PubMed ID: 19056394. Show all entries for this paper.

Displaying record number 58603

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Pol(328-336)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9
Species (MHC/HLA)	human(B*3501)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes that this is an optimal B*3501 epitope based on <cite>Westrop2009</cite>.

References

Displaying record number 58652

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(216-224)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	Gag HA9
Subtype	B, C
Species (MHC/HLA)	human(B*3501)
Immunogen	HIV-1 infection
Country	Barbados, Botswana, Haiti, Japan, Mexico, South Africa, United Kingdom, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Intracellular cytokine staining, Tetramer binding
Keywords	subtype comparisons, optimal epitope, novel epitope

Notes

While host HLA Class I genotype is the major genetic determinant of HIV-1 progression to AIDS, the same HLA allele could have varying outcomes for different infecting HIV clades. Overall, p24 Gag-specific epitopes were targeted significantly more frequently by C-clade-infected B*3501-positive subjects (55%) than B-clade-carrying B*3501-subjects (31%), while Env-specific epitopes were targeted more frequently by B-clade-infected subjects.
In general HLA-B*3501-restricted epitopes, were not targeted differentially for different clades. In contrast, CTL targeting against B*3501-restricted clade C Gag epitope, NPPIPVGDIY (NY10) but not clade B NY10, was associated with a lower viral set point and higher absolute CD4 count, i.e. better disease control. The above major result for epitope NY10 was confirmed for the B clade variant in Caucasian, Japanese and Mexican cohorts; C clade results were confirmed in South African (Durban) and Botswanan (Gaborne) cohorts.
In addition 5 new C-clade epitopes were identified.
Novel epitope, Gag HA9, HPVHAGPIA, was confirmed as an optimal epitope restricted by HLA-B*3501. Strong binding avidity to B*3501 was determined and CTL response was detected in >40% of B- and >50% of C-clade infected subjects.

References

Matthews2012 Philippa C. Matthews, Madoka Koyanagi, Henrik N. Kløverpris, Mikkel Harndahl, Anette Stryhn, Tomohiro Akahoshi, Hiroyuki Gatanaga, Shinichi Oka, Claudia Juarez Molina, Humberto Valenzuela Ponce, Santiago Avila Rios, David Cole, Jonathan Carlson, Rebecca P. Payne, Anthony Ogwu, Alfred Bere, Thumbi Ndung'u, Kamini Gounder, Fabian Chen, Lynn Riddell, Graz Luzzi, Roger Shapiro, Christian Brander, Bruce Walker, Andrew K. Sewell, Gustavo Reyes Teran, David Heckerman, Eric Hunter, Søren Buus, Masafumi Takiguchi, and Philip J. R. Goulder. Differential Clade-Specific HLA-B*3501 Association with HIV-1 Disease Outcome Is Linked to Immunogenicity of a Single Gag Epitope. J. Virol., 86(23):12643-12654, Dec 2012. PubMed ID: 22973023. Show all entries for this paper.

Displaying record number 60679

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	p24(216-224)
Epitope	`HPVHAGPIA`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*3501)
Immunogen	HIV-1 infection
Patient MHC/HLA	S2:
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	dendritic cells, assay or method development, memory cells

Notes

In general, mature IL-12p70-producing dendritic cells (DC) that are responsive to CD40L and loaded with inactive autologous HIV-1 were found to prime naive CTL to respond to a far broader range of conserved and variable Gag peptides than DC-stimulated memory T cells could. Stimulated memory CTL also had lower anti-CD4 T-cell cytolytic function than primed naive CTL. A novel in vitro model of DC immunotherapy was established.
Subject S2 reacted to autologous Gag epitope HPVHAGPIA, part of peptides AAEWDRVHPVHAGPIAPG and DRVHPVHAGPIAPGQMRE which elicited responses of 709 SFC/106 cells from DC-primed naive T cells versus 659 from primed memory cells but contrary to most cases, the second peptide elicited 384 SFC/106 cells from naive cells as opposed to 1659 from DC-stimulated memory T cells.

References

Smith2016 Kellie N. Smith, Robbie B. Mailliard, Paolo A. Piazza, Will Fischer, Bette T. Korber, Ronald J. Fecek, Deena Ratner, Phalguni Gupta, James I. Mullins, and Charles R. Rinaldo. Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells. MBio, 7(3), 31 May 2016. PubMed ID: 27247230. Show all entries for this paper.

Displaying record number 59767

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(216-224)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9
Species (MHC/HLA)	human(B3502, B3503, B*5301)
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.
HPVHAGPIA had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 15/37 B*3502,B*3503,B*5301-positive subjects and 63/304 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 56438

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	p24
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9(p24)
Subtype	B
Species (MHC/HLA)	human(B39, B7)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords

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.
Although the tested peptide sequence contains the exact sequence of a previously described HLA-B7 and -B39 optimal epitope, HPVHAGPIA, none of the 9 HLA-B7 carriers responded to it (author communication and Fig.1). No information regarding HLA-B39 reactivity is provided.

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.

Displaying record number 53971

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`HPVHAGPIA`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*3910)
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.
HPVHAGPIA is an optimal epitope.

References

Displaying record number 59768

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(216-224)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9
Species (MHC/HLA)	human(B*55)
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.
HPVHAGPIA had a significantly positive association with HLA B*55; it was recognized by 2/2 B*55-positive subjects and 37/232 B*55-negative subjects.

References

Displaying record number 54333

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	B7-HA9(Gag)
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 56545

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	Gag237
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	vaccine
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine component	Other

Notes

DNA vaccine EP HIV-1090 evaluation in patients receiving ART was done. This vaccine is composed of multiple CTL epitopes, all associated with certain HLA supertypes. Differences of CTL response rate in vaccine and placebo recipients however, was not significant.
HPVHAGPIA is a Gag epitope encoded in the EP HIV-1090 polyepitope vaccine.

References

Wilson2008 Cara C. Wilson, Mark J. Newman, Brian D. Livingston, Samantha MaWhinney, Jeri E. Forster, Jim Scott, Robert T. Schooley, and Constance A. Benson. Clinical Phase 1 Testing of the Safety and Immunogenicity of an Epitope-Based DNA Vaccine in Human Immunodeficiency Virus Type 1-Infected Subjects Receiving Highly Active Antiretroviral Therapy. Clin. Vaccine Immunol., 15(6):986-994, Jun 2008. PubMed ID: 18400976. Show all entries for this paper.

Displaying record number 57963

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	p24(84-92)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	immunodominance, elite controllers

Notes

Immunodominant responses were identified from progressors and controllers. Epitope-specific CD8 T-cell lines from progressors and controllers had similar effector function profiles in intracellular cytokine staining assays. In contrast, CD8 T-cell lines derived from controllers showed enhanced virus suppression when compared with progressors. Virus suppression was mediated in an MHC-dependent manner and found to correlate with a polyfunctional IL-2+ CD8 T-cell response.
HPVHAGPIA was one of 15 immunodominant responses identified, and a T-cell line was isolated from a B7-positive progressor patient who was highly responsive to it.

References

Akinsiku2011 Olusimidele T. Akinsiku, Anju Bansal, Steffanie Sabbaj, Sonya L. Heath, and Paul A. Goepfert. Interleukin-2 Production by Polyfunctional HIV-1-Specific CD8 T Cells Is Associated with Enhanced Viral Suppression. J. Acquir. Immune Defic. Syndr., 58(2):132-140, 1 Oct 2011. PubMed ID: 21637109. Show all entries for this paper.

Displaying record number 53548

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(216-224)
Epitope	`HPVHAGPIA`	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 52158

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	p24(84-92)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	B7-HA9
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 55720

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9-B09
Subtype	B, F
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	Argentina
Experimental methods
Keywords	dynamics, HLA associated polymorphism

Notes

Dynamics of CTL escape mutations was studied theoretically by analyzing plasma samples from 302 subjects (collected over 20 years). HLA associated polymorphisms accumulated in a subtype-specific manner.
Epitope HPVHAGPIA with anchor residues at H(P)VHAGPIA mutates to variant HPaHAGPvA and HPVHAGPvA; the latter increases over time.

References

Dilernia2008 Dario Alberto Dilernia, Leandro Jones, Sabrina Rodriguez, Gabriela Turk, Andrea E Rubio, Sandra Pampuro, Manuel Gomez-Carrillo, Christian Bautista, Gabriel Deluchi, Jorge Benetucci, María Beatriz Lasala, Leonardo Lourtau, Marcelo Horacio Losso, Héctor Perez, Pedro Cahn, and Horacio Salomón. HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations. PLoS ONE, 3(10):e3429, 2008. PubMed ID: 18941505. Show all entries for this paper.

Displaying record number 55200

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location
Epitope	`HPVHAGPIA`	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), an additional HLA (B55) was statistically predicted to be associated with this optimal epitope, HPVHAGPIA.

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 59769

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag(216-224)
Epitope	`HPVHAGPIA`	Epitope Alignment
Epitope Name	HA9
Species (MHC/HLA)	human(C*12)
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.
HPVHAGPIA had a significantly positive association with HLA C*12; it was recognized by 14/44 C*12-positive subjects and 39/234 C*12-negative subjects.

References

Displaying record number 58202

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag/Pol(216- CDC-451)
Epitope	`HPVHAGPIA`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	computer prediction
Experimental methods
Keywords	T-cell crossreactivity to human proteins

Notes

The paper defines potential crossreactivity between HIV-1 and human host proteins. HIV B-clade strain CDC-451 shares 50 7mers and 3 8mers with the human proteome. Of these, 35 are within experimentally-validated epitopes targeted by human immune responses to HIV. The number of common 7mers between the proteomes is 3.7-fold higher than would be expected by chance.
The 7mers in common with HIV are present in human proteins that, when altered, are associated with AIDS-related symptoms, suggesting that disease symptoms may be caused by autoimmune responses.
Previously-documented CTL epitope HPVHAGPIA contains 7mer PVHAGPI, which occurs in human gene PTPRE: Receptor-type tyrosine-protein phosphatase epsilon.

References

Lucchese2011 Guglielmo Lucchese, Angela Stufano, Michele Calabro, and Darja Kanduc. Charting the Peptide Crossreactome between HIV-1 and the Human Proteome. Front. Biosci. (Elite Ed.), 3E:1385-1400, 2011. PubMed ID: 21622144. Show all entries for this paper.

Displaying record number 58035

HXB2 Location	Gag(216-224) p24(84-92) DNA(1435..1461)	Gag Epitope Map
Author Location	Gag
Epitope	`HPVHAGPIA`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	vaccine
Patient MHC/HLA	A3301, A7401, B5301, B7801, Cw0401, Cw1601
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.
1 vaccinee recognized 9mer HPVHAGPIA.

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.