Search CTL/CD8+ T-Cell Epitope Database

Found 13 matching records:

Displaying record number 60156

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	RL10
Species (MHC/HLA)	human(A*80)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

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.
RPAEPVPLQL had a significantly positive association with HLA A*80; it was recognized by 1/1 A*80-positive subjects and 6/302 A*80-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 54797

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	RL10
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods	CTL suppression of replication
Keywords	class I down-regulation by Nef

Notes

The impact of Nef on antiviral activity was studied. CTL-targeting epitopes were susceptible to the effects of Nef, both in late (Gag, RT, Env) and in early proteins (Rev, Nef), although to a lesser degree in early proteins. HLA-C-restricted CTLs (unlike HLA-A and HLA-B) were unaffected by Nef both in early (Nef) and late (Env) proteins.
Late protein Rev epitope RPAEPVPLQL-recognizing CTLs were affected by Nef.

References

Adnan2006 Sama Adnan, Arumugam Balamurugan, Alicja Trocha, Michael S. Bennett, Hwee L. Ng, Ayub Ali, Christian Brander, and Otto O. Yang. Nef Interference with HIV-1-Specific CTL Antiviral Activity Is Epitope Specific. Blood, 108(10):3414-3419, 15 Nov 2006. PubMed ID: 16882705. Show all entries for this paper.

Displaying record number 55517

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev
Epitope	`RPAEPVPLQL`	Epitope Alignment
		Show epitope variants
Epitope Name	RL10
Subtype	A, B, C, D, F, G
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Chromium-release assay, Other
Keywords	subtype comparisons

Notes

Cross-clade CTL epitope recognition was tested for functional responses by CTL suppression using endogenously derived cell-surface epitopes rather than supraphysiologic exogenously added peptide epitopes. Functional avidity was actually diminished in non-autologous clade epitopes, calling into question current methods for assessing cross-clade or standard CTL activity and therefore vaccine design.
RL10 epitope variants used were RPAEPVPLQL for clades B/C/G, RSAEPVPLQL for clade A1, RPTEPVPLQL for clades A2/F2, RSEEPVPLQL for clade D, and RPEEPVPLQL for clade F1. Clade B-elicited CTLs recognized epitopes from all other clades when tested by Cr-release. Suppression of HIV replication however, as well as functional avidity were reduced for different clade consensus epitope sequences.

References

Bennett2008 Michael S. Bennett, Hwee L. Ng, Ayub Ali, and Otto O. Yang. Cross-Clade Detection of HIV-1-Specific Cytotoxic T Lymphocytes Does Not Reflect Cross-Clade Antiviral Activity. J. Infect. Dis., 197(3):390-397, 1 Feb 2008. PubMed ID: 18184090. Show all entries for this paper.

Displaying record number 62760

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
		Show epitope variants
Epitope Name	RL10
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	in vitro stimulation or selection
Experimental methods	Chromium-release assay, Cytokine production, Gene expression assay/analyses, Other
Keywords	characterizing CD8+ T cells

Notes

In this first study to directly investigate the role of weak agonist epitope variant-induced anergy in HIV-1-specific CTL function, variants with lower functional avidities, relative to index epitopes SLYNTVATL (SL9, HLA-A*02-restricted), RPAEPVPLQL (RL10, HLA-B*07-restricted), & KRWIIMGLNK (KK10, HLA-B*27-restricted), unexpectedly did not induce anergy or cytolytic dysfunction in CTL clones.
A RL10-specific CTL clone stimulated by index epitope RPAEPVPLQL, compared to lower functional avidity variants RPvEPVPLQL or RPtEPVPfhL, demonstrated stronger cytolytic function, cytokine production (IFNγ, TNFα, MIP-1α, & MIP-1β) and differential gene expression.
CTL clone pre-stimulation with RPvEPVPLQL or RPtEPVPfhL had no impact on RPAEPVPLQL-specific cytolytic function.

References

Grossman2019 Mark A. Grossman, Christian Hofmann, Hwee L. Ng, and Otto O. Yang. Suboptimal Stimulation by Weak Agonist Epitope Variants Does Not Drive Dysfunction of HIV-1-Specific Cytotoxic T Lymphocyte Clones. AIDS, 33(10):1565-1574, 1 Aug 2019. PubMed ID: 31306165. Show all entries for this paper.

Displaying record number 60154

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	RL10
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, chronic infection

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.
RPAEPVPLQL had a significantly positive association with HLA B*07; it was recognized by 5/38 B*07-positive subjects and 7/303 B*07-negative subjects.

References

Displaying record number 54088

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	RL10
Species (MHC/HLA)	human(B*07)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

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 59048

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	RL10-Rev
Subtype	B, C
Species (MHC/HLA)	human(B*07:02)
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 RL10, RPAEPVPLQL, a B- and C-clade Rev epitope was targeted more by B-clade infected subjects than by C-clade infected individuals. The B-clade and C-clade consensus epitope is the same. Binding affinity of RL10 to B*0702 was K_d = 65 nM. RL10 is contained within OLP102, ILSTCLGRPAEPVPLQL.

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 61162

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
		Show epitope variants
Epitope Name	RL10
Subtype	B
Species (MHC/HLA)	human(B*07:02)
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.
Rev epitope RPAEPVPLQL, RL10_66-75,-specific T cells were less cytotoxic to variants than autologous RL10 in acute infection. 3/5 variants tested did cross-react with T cells specific to autologous RL10.

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 58712

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	Rev-RL10
Subtype	C
Species (MHC/HLA)	human(B*42:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	A30:01, B42:02, C*17:01
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.
An 18-mer peptide containing Rev epitope RL10, RPAEPVPLQL, was recognized by B*4202-positive responding subjects versus 0% 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 54760

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	RL10
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods	Chromium-release assay, Other
Keywords	binding affinity

Notes

Standard assays like ELISpot, ICS and tetramer staining do not measure antiviral activity of HIV-infected CTLs, but use exogenous synthetic peptides on uninfected cells, or HLA tetramers. Similarly, functional avidity assesses CTL activity against uninfected target cells. Here functional avidity is compared to the efficiency of actual infected cells' recognition and killing, revealing a sharp threshold between CTL immune antiviral activity and lack of infected cell recognition.
As previously shown, epitopes and their variants spanned orders of magnitude of SD50. Likewise, CTL clearance of infected cells varied from 0 to 100% with epitope sequence variation. Moreover, direct suppression of HIV-1 replication by CTLs also varied with epitope variant.
When killing efficiency (KE) using virus-infected cells was compared to functional avidity using synthetic peptides, there was a narrow threshold separating maximal killing from almost none. Since different SL9-specific clones had similar KEs, which were vastly different from RL10-specific CTL KEs, it was obvious that KEs varied with epitope sequence too. Finally, a strong correlation between KE and inhibition of viral replication was also seen.
This epitope, RPAEPVPLQL, showed marked differences in its functional avidity, killing efficiency, as well as inhibition of viral replication when compared to its variants RsAEPVPLQL, RPtEPVPLQL, RPeEPVPLQL, RPAqPVPLQL, RPAEPVPLhL, RPAEPVPfQL, RPvEPVPLQL, RPeEPVPfQL, RPeEPVPLpL, RPAEPVPfhL, RPtEPVPfQL, RPtEPVPLeL, RPqEPVPLlL and RPtEPVPfhL.

References

Bennett2007 Michael S. Bennett, Hwee L. Ng, Mirabelle Dagarag, Ayub Ali, and Otto O. Yang. Epitope-Dependent Avidity Thresholds for Cytotoxic T-Lymphocyte Clearance of Virus-Infected Cells. J. Virol., 81(10):4973-4980, May 2007. PubMed ID: 17329324. Show all entries for this paper.

Displaying record number 60995

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	17543: A01:01, A02:02, B07:02, B15:03, C02:10, C07:02
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.
RPAEPVPLQL, restricted by B7, was recognized by 1 patient 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 60155

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	RL10
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, chronic infection

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.
RPAEPVPLQL had a significantly positive association with HLA C*12; it was recognized by 3/46 C*12-positive subjects and 1/241 C*12-negative subjects.

References

Displaying record number 60157

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HXB2 Location	Rev(66-75) DNA(8498..8527)	Rev Epitope Map
Author Location	Rev(66-75)
Epitope	`RPAEPVPLQL`	Epitope Alignment
Epitope Name	RL10
Species (MHC/HLA)	human(C*17)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

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.
RPAEPVPLQL had a significantly positive association with HLA C*17; it was recognized by 2/15 C*17-positive subjects and 4/287 C*17-negative subjects.