Search CTL/CD8+ T-Cell Epitope Database

Found 37 matching records:

Displaying record number 60235

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Species (MHC/HLA)	human(A*23)
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.
RYPLTFGW had a significantly positive association with HLA A*23; it was recognized by 10/17 A*23-positive subjects and 24/243 A*23-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 57845

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Subtype	B
Species (MHC/HLA)	human(A23, A24, B35, B53)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, TCR binding
Keywords	rate of progression, TCR usage, optimal epitope

Notes

The study measured the functional avidities of HIV-specific CTL responses targeting 20 optimally defined CTL epitopes in a cohort of 44 HIV controllers and 68 non-controllers. Highest functional avidities were toward HLA-B-restricted epitopes in Gag. Avidities were higher in HIV controllers than non-controllers. Higher-avidity T-cell populations had narrower TCR repertoires.
Promiscuously-presented epitope RW8 (A23, A24, B35, B53) exhibited lower functional avidity in the context of the HLA alleles associated with poorer disease outcome (B35, B53).

References

Berger2011 Christoph T. Berger, Nicole Frahm, David A. Price, Beatriz Mothe, Musie Ghebremichael, Kari L. Hartman, Leah M. Henry, Jason M. Brenchley, Laura E. Ruff, Vanessa Venturi, Florencia Pereyra, John Sidney, Alessandro Sette, Daniel C. Douek, Bruce D. Walker, Daniel E. Kaufmann, and Christian Brander. High-Functional-Avidity Cytotoxic T Lymphocyte Responses to HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV Control. J. Virol., 85(18):9334-9345, Sep 2011. PubMed ID: 21752903. Show all entries for this paper.

Displaying record number 53949

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	( C consensus)
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(A*23:01)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	epitope processing, 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.
Mutational patterns in a residue outside of the optimized epitope of RYPLTFGW are associated with the presence of the HLA presenting molecule in the host.

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 53279

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	( C consensus)
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(A*23:01)
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 56237

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(A*23:01, A24)
Immunogen	HIV-1 infection
Patient MHC/HLA	A23:01, A29:02, B15:10, B45:01, C06:02, C16:01; A23:01, A29:02, B41:01, B42:01, C*17:01
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	rate of progression, immunodominance

Notes

47 HIV-1 subtype C infected patients were followed longitudinally to determine whether there was a relation between magnitude and breadth of CTL responses in primary, acute infection (measured by IFN-gamma ELISpot) and disease progression (measured as viral load at 12 months). CTL responses to Nef were dominant (targeting 6 epitopic regions), followed by responses to Gag, Pol, Rev, Vpr, Env, Vpu, Vif and finally Tat.
RYPLTFGW is a known HLA-A*2301 and -A24-restricted epitope that is part of peptide PGPGVRYPLTFGWCFKLVP which elicited the most dominant response in 8/10 patients. Response to a peptide containing this epitope was detected in both an early controller and 2 rapid progressors 12 weeks post-infection.

References

Gray2009 Clive M. Gray, Mandla Mlotshwa, Catherine Riou, Tiyani Mathebula, Debra de Assis Rosa, Tumelo Mashishi, Cathal Seoighe, Nobubelo Ngandu, Francois van Loggerenberg, Lynn Morris, Koleka Mlisana, Carolyn Williamson, Salim Abdool Karim, and CAPRISA 002 Acute Infection Study Team. Human Immunodeficiency Virus-Specific gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point. J. Virol., 83(1):470-478, Jan 2009. PubMed ID: 18945774. Show all entries for this paper.

Displaying record number 56607

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Subtype	C
Species (MHC/HLA)	human(A23:01, A24:02)
Immunogen	HIV-1 infection
Country	South Africa, Zambia
Experimental methods
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

A cohort of clade C-infected Zambian HIV-1 transmission pairs was studied. Accumulation in the donor of HLA-B restricted mutations in Gag, but not in Nef resulted in a reduced viral load in a recipient upon transmission.
20 mutations in Gag and 11 mutations in Nef, within or flanking CTL epitopes, were considered based on data from a Clade C South African cohort. HLA-A*2402-restricted RYPLTFGW (RW8) was associated with a polymorphism at R(Y)PLTFGW, and HLA-A*2301-restricted RW8 was associated with a polymorphism flanking it at PGVRYPLTFGWC(F)KL.

References

Goepfert2008 Paul A. Goepfert, Wendy Lumm, Paul Farmer, Philippa Matthews, Andrew Prendergast, Jonathan M. Carlson, Cynthia A. Derdeyn, Jianming Tang, Richard A. Kaslow, Anju Bansal, Karina Yusim, David Heckerman, Joseph Mulenga, Susan Allen, Philip J. R. Goulder, and Eric Hunter. Transmission of HIV-1 Gag Immune Escape Mutations Is Associated with Reduced Viral Load in Linked Recipients. J. Exp. Med., 205(5):1009-1017, 12 May 2008. PubMed ID: 18426987. Show all entries for this paper.

Displaying record number 58545

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	A24-RW8
Subtype	B
Species (MHC/HLA)	human(A*24)
Immunogen	HIV-1 infection
Country	United States
Experimental methods
Keywords	review, rate of progression, acute/early infection

Notes

Acute infection with HIV-1 is accompanied by high viral load (VL) and loss of CD4 helper T cells. Early inhibition of VL by CTL results in a 'set point' that is correlated with disease progression. The early CTL response during acute infection if successful is to a known immunodominant epitope. Following, chronic infection sets in with a greater breadth and magnitude of CTL response, but no change in VL or HIV-1 replication. Immunodominant epitopes from several studies that help set a lower VL during acute phase are listed in this review.
RYPLTFGW, A24-RW8, when restricted by HLA-A*24 is recognized by 50% acutely-infected and 36% chronically-infected North American subjects expressing the same HLA allele. HLA-A*24 is present at a frequency of 21.3% in North American white populations.

References

Streeck2010 Hendrik Streeck and Douglas F. Nixon. T Cell Immunity in Acute HIV-1 Infection. J. Infect. Dis., 202(Suppl 2):S302-8, 15 Oct 2010. PubMed ID: 20846037. Show all entries for this paper.

Displaying record number 60236

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Species (MHC/HLA)	human(A*24)
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.
RYPLTFGW had a significantly positive association with HLA A*24; it was recognized by 9/27 A*24-positive subjects and 7/199 A*24-negative subjects.

References

Displaying record number 61603

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef
Epitope	`RYPLTFGW`	Epitope Alignment
		Show epitope variants
Epitope Name	A24-RW8 Nef
Species (MHC/HLA)	human(A*24)
Immunogen	HIV-1 infection
Patient MHC/HLA	9213: A01, A24, B38, B44, C*04
Experimental methods	Other
Keywords	escape

Notes

Proof of principle is given to show that HIV-1 genome sequence from short reads can be used to reconstruct actual whole genome haplotypes including immune escape mutations. 30 whole genome haplotypes from subject 9213 were reconstructed longitudinally and published. Mutations are found to change depending on linkage and resulting clonal interference shows that selection coefficients to study HIV evolution must be estimated for complete haplotypes and not individual escapes.
Dominant Nef epitope, RW8, RYPLTFGW was present as WT in haplotypes studied, at days 0-165, but by day 59 had begun escape for Patient 9213. Mutations seen were RYPLmFGW (T5M), RYPLTlGW (F6L) and anchor residue change, RfPLTFGW (Y2F).

References

Pandit2014 Aridaman Pandit and Rob J. de Boer. Reliable Reconstruction of HIV-1 Whole Genome Haplotypes Reveals Clonal Interference and Genetic Hitchhiking among Immune Escape Variants. Retrovirology, 11:56, 4 Jul 2014. PubMed ID: 24996694. Show all entries for this paper.

Displaying record number 56399

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Subtype	B
Species (MHC/HLA)	human(A*24)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	viral fitness and reversion, 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.
HLA-A*24-associated substitutions within optimally defined epitope RYPLTFGW are at positions Y2 and F6, RyPLTfGW. Codon 135, i.e. RW8 position Y2 was the most rapidly reverting Nef epitope-associated mutation.

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 55193

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location
Epitope	`RYPLTFGW`	Epitope Alignment
Species (MHC/HLA)	human(A24)
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.
Based on a prediction of the minimum number of HLA alleles needed to cover the HLA representation in all responders to this optimal epitope, a minimum set of 6 alleles was found: 1 allele previously known to be associated (A24) and 5 additional alleles (A01, A02, A23, Cw04, Cw07).

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 55021

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location
Epitope	`RYPLTFGW`	Epitope Alignment
Species (MHC/HLA)	human(A24)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	binding affinity, immunodominance, optimal epitope

Notes

CTL responses were tested for both HIV-1 and EBV derived epitopes restricted by HLA-A, -B and -C alleles. HLA-B alleles more frequently induce detectable responses and that the responses are generally of greater magnitude than those for HLA-A and -C alleles.
The magnitude and frequency of CTL recognition were related to each other and that TCR avidity for HLA/peptide complexes is a more important determinant for magnitude of response than peptide binding affinity to HLA.
EBV response patterns were not significantly altered by HIV coinfection.
Epitope KTKPPLPSVKK elicited a magnitude of response of 252 SFC with a functional avidity of 0.001nM.

References

Bihl2006 Florian Bihl, Nicole Frahm, Loriana Di Giammarino, John Sidney, Mina John, Karina Yusim, Tonia Woodberry, Kaori Sango, Hannah S. Hewitt, Leah Henry, Caitlyn H. Linde, John V. Chisholm, III, Tauheed M. Zaman, Eunice Pae, Simon Mallal, Bruce D Walker, Alessandro Sette, Bette T. Korber, David Heckerman, and Christian Brander. Impact of HLA-B Alleles, Epitope Binding Affinity, Functional Avidity, and Viral Coinfection on the Immunodominance of Virus-Specific CTL Responses. J. Immunol., 176(7):4094-4101, 1 Apr 2006. PubMed ID: 16547245. Show all entries for this paper.

Displaying record number 54261

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	A24-WR8(Nef)
Species (MHC/HLA)	human(A24)
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 contributions of immune responses restricted to individual HLA class I molecules were studied.
This epitope-HLA combination was recognized. The most frequently recognized 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 contributions 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 52275

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	A24-RW8(Nef)
Subtype	B
Species (MHC/HLA)	human(A24)
Immunogen	HIV-1 infection
Patient MHC/HLA	A24, B27, B7
Experimental methods
Keywords	HAART, ART, supervised treatment interruptions (STI)

Notes

Peripheral blood (PB) and lymph node (LN) CD8+ T-cell responses were compared in 15 asymptomatic HIV-1 infected patients using all known optimal CTL epitopes (http://hiv-web.lanl.gov/content/hiv-db/REVIEWS/brander2001.html) for each person's class I HLA alleles.
60 epitope responses were detected in both PB and LN samples of the 15 patients, and an additional 8 responses were detected only in LN. The total magnitude of the response was similar in LN and PB, but the percentage of CD8+ T cells in the LN is lower so the number of HIV-specific cells per million CD8+ T-cells is higher in the LN.
1 year post-HAART treatment in five patients studied, the magnitude of the CD8 T-cell response was decreased in both LN and PB, but more dramatically in PB, and 13/25 epitope responses in the PB became undetectable, in contrast to 5/26 in the LN.
Treatment interruption following HAART induced resulted in increased viremia accompanied by the restoration of the detection of 13 epitopes that had become undetectable in the PB, and the addition of 9 novel epitope responses.
Breakdowns of epitope responses were shown for 4 individuals. Patient C displayed the greatest response to B27-KK10(p24), and in decreasing order also responded to A24-RW8(Nef), B7-IL9(gp41), A24-RL9(gp41), A24-YL8(gp41), and B7-TM9(Nef).

References

Altfeld2002 Marcus Altfeld, Jan van Lunzen, Nicole Frahm, Xu G. Yu, Claus Schneider, Robert L. Eldridge, Margaret E. Feeney, Dirk Meyer-Olson, Hans-Juergen Stellbrink, and Bruce D. Walker. Expansion of Pre-existing, Lymph Node-localized CD8+ T Cells During Supervised Treatment Interruptions in Chronic HIV-1 Infection. J. Clin. Invest., 109(6):837-843, Mar 2002. PubMed ID: 11901192. Show all entries for this paper.

Displaying record number 1543

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(138-147 SF2)
Epitope	`RYPLTFGW`	Epitope Alignment
Species (MHC/HLA)	human(A24)
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-A24+ individuals that had a CTL response to this epitope broken down by group: 0/0 group 1, 2/3 group 2, and 0/0 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 62163

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	Nef-RW8
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review, escape, HLA associated polymorphism

Notes

This review focuses on HLA associated polymorphisms and how studying HIV adaptation in the context of HLA can show us epitopes that are well conserved with high mutational barriers to escape as well as epitopes that are extensively mutated in circulation within some populations and viral subtypes.
In >80% subtype B-infected, HLA-A*2402-expressing subjects, the Nef-Y135F polymorphism is seen. Y135F is found within the epitope Nef-RW8, RYPLTFGW, conferring partial escape from CTL response. [Sun et al. Cell Rep. 15(10): 2279-2291 (2016)].

References

Avila-Rios2019 Santiago Avila-Rios, Jonathan M. Carlson, Mina John, Simon Mallal, and Zabrina L. Brumme. Clinical and Evolutionary Consequences of HIV Adaptation to HLA: Implications for Vaccine and Cure. Curr. Opin. HIV AIDS, 14(3):194-204, May 2019. PubMed ID: 30925534. Show all entries for this paper.

Displaying record number 1132

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(138-147 LAI)
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is an A*2402 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 54189

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(169-176)
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(A*24:02)
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.
RYPLTFGW was a previously defined A*2402 presented epitope that encompassed an A*24 associated polymorphism, RyPLTFGW, in the second 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 54755

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef
Epitope	`RYPLTFGW`	Epitope Alignment
Species (MHC/HLA)	human(A*24:02)
Immunogen	peptide-HLA interaction
Experimental methods	Tetramer binding
Keywords	binding affinity

Notes

MHC can exert a protective effect on HIV-1 disease progression by the interaction of MHC Class I molecules with Killer Inhibitory Receptors (KIR) of the innate immune system. Here, KIR3DS1, a putative stimulatory receptor and allele of the inhibitory KIR3DL1, is studied. Bw4 MHC Class I proteins were implicated in this KIR's ligand specificity, but the authors were unable to generate binding of Bw4Ile80 tetramers in complex with epitopes to KIR3DS1 transiently expressed on 293-T cells, using a panel of HIV-epitopes differing at p7 and p8.
This epitope, RYPLTFGW (MHC Class I restriction, serotype Bw4) complexed with MHC A*2402 as a tetramer was unable to bind KIR3DS1 at 4, 20 and 37C. However, the A*2402-KYKLKHIVW complex does bind inhibitory KIR3DL1 subtype KIR3DL1*005.

References

Gillespie2007 Geraldine M. A. Gillespie, Arman Bashirova, Tao Dong, Daniel W. McVicar, Sarah L. Rowland-Jones, and Mary Carrington. Lack of KIR3DS1 Binding to MHC Class I Bw4 Tetramers in Complex with CD8+ T Cell Epitopes. AIDS Res. Hum. Retroviruses, 23(3):451-455, Mar 2007. PubMed ID: 17411378. Show all entries for this paper.

Displaying record number 57249

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef
Epitope	`RYPLTFGW`	Epitope Alignment
		Show epitope variants
Epitope Name	RW8
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, CD8 T-cell Elispot granzyme B
Keywords	acute/early infection

Notes

Responses to CTL epitope variants were tested in newly-infected patients and in vaccine recipients.
In a newly-infected patient, 2 variants of RYPLTFGW were recognized by IFNg EliSpot and Granzyme B EliSpot: RYPLTFGW, RfPLTFGW.
3 variants with semi-conservative substitutions in presumed TCR contact sites RYPLTlGW, RYPLcFGW, RfPLcFGW were not recognized neither by IFNg EliSpot nor Granzyme B EliSpot.

References

Malhotra2009 U. Malhotra, J. Nolin, H. Horton, F. Li, L. Corey, J. I. Mullins, and M. J. McElrath. Functional Properties and Epitope Characteristics of T-Cells Recognizing Natural HIV-1 Variants. Vaccine, 27(48):6678-6687, 12 Nov 2009. PubMed ID: 19747576. Show all entries for this paper.

Displaying record number 58986

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(131-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Country	Australia, Canada, Spain, Switzerland
Experimental methods	Other
Keywords	mutation acquisition

Notes

Computational genome-wide scans were run to find associations between (subjects' ) host genome DNA polymorphisms, and infecting HIV-1 genome sequence variation from 1071 subjects, as well as their viral load (VL). Such genome-to-genome approaches also reveal sites of single nucleotide polymorphisms (SNPs) linked to variant HIV-1 amino acids that either limit viral efficiency or that are easily tolerated by it.
48 amino acid residues of HIV-1 were linked to human SNPs, and the variants were not antiretroviral drug resistance mutations. 50% of these viral amino acids were located within previously defined optimal epitopes, such as RYPLTFGW, whose variation at position 135 is associated with SNP rs72845950.

References

Bartha2013 István Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. McLaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martinez-Picado, Judith Dalmau, Cecilio López-Galíndez, Concepción Casado, Andri Rauch, Huldrych F. Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O'Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolo Fusi, Zoltán Kutalik, Todd M. Allen, Viktor Müller, P. Richard Harrigan, David Heckerman, Amalio Telenti, and Jacques Fellay. A Genome-to-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Viral Control. eLife, 2:e01123, 2013. PubMed ID: 24171102. Show all entries for this paper.

Displaying record number 59313

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(138-145)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	Chromium-release assay, Relative replication capacity assay, TCR binding, Tetramer binding
Keywords	TCR usage, structure

Notes

Two overlapping A*2402-restricted epitopes were studied. RF10(RYPLTFGWCF)-specific and RW8(RYPLTFGW)-specific CTLs had different TCR repertoires and had no overlapping antigen reactivity or clonotypic compositions. Crystallography revealed important structural differences between RW8 and RF10 in complex with A*2402.
14/23 A*2402-positive, drug-naive HIV-1-infected subjects were positive for RW8-specific CTLs. EC₅₀ of RW8-specific CTL for binding to TCR was higher than that of RF10-cells.

References

Sun2014 Xiaoming Sun, Mamoru Fujiwara, Yi Shi, Nozomi Kuse, Hiroyuki Gatanaga, Victor Appay, George F. Gao, Shinichi Oka, and Masafumi Takiguchi. Superimposed Epitopes Restricted by the Same HLA Molecule Drive Distinct HIV-Specific CD8+ T Cell Repertoires. J. Immunol., 193(1):77-84, 1 Jul 2014. PubMed ID: 24899498. Show all entries for this paper.

Displaying record number 59375

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	P07: A24:02, A68:01, B18:01, B35:01, C07:01, C07:04
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction, optimal epitope

Notes

Peptides of 15-20 amino acids were used to compare epitopes determined experimentally versus predictions from 3 epitope prediction tools: SYFPEITHI, CTLPRED, and IEDB. The IEDB tool performed best, but none of the tools performed well. Predictions were better when the HLA restriction of the peptide was known, and when the restricting HLA was present at high frequency in the population.
RYPLTFGW was an optimal epitope experimentally mapped from the input peptide PDWQNYTPGPGVRYPLTFGW.

References

Roider2014 Julia Roider, Tim Meissner, Franziska Kraut, Thomas Vollbrecht, Renate Stirner, Johannes R. Bogner, and Rika Draenert. Comparison of Experimental Fine-Mapping to In Silico Prediction Results of HIV-1 Epitopes Reveals Ongoing Need for Mapping Experiments. Immunology, 143(2):193-201, Oct 2014. PubMed ID: 24724694. Show all entries for this paper.

Displaying record number 60668

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-)
Epitope	`RYPLTFGW`	Epitope Alignment
		Show epitope variants
Epitope Name	RW8, Nef134-8
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	Other, Tetramer binding
Keywords	rate of progression, escape

Notes

Y135F adapted HIV-1 is an escape from HLA-A*2402, the most common Japanses HLA allele. When this escape is the infecting virus, rapid disease ensues in a cohort of 21 adults, suggesting the strong impact of pathogen (HIV-1) adaptation to population level host pressures (HLA).
Two overlapping epitopes, RYPLTFGW, RW8 or Nef 134-8 and RYPLTFGWCF, RW10 or Nef 134-10, and their Y135F variants bind A*2402 in the following order: Nef134-10 > Nef134-10.Y135F > Nef134-8 > Nef134-8.Y135F.

References

Katoh2016 Jiro Katoh, Ai Kawana-Tachikawa, Akihisa Shimizu, Dayong Zhu, Chungyong Han, Hitomi Nakamura, Michiko Koga, Tadashi Kikuchi, Eisuke Adachi, Tomohiko Koibuchi, George F. Gao, Zabrina L. Brumme, and Aikichi Iwamoto. Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population. PLoS One, 11(3):e0150397, 2016. PubMed ID: 26953793. Show all entries for this paper.

Displaying record number 61002

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	44091: A02:01:01G, A24:02:01G, B44:02:01G, B57:01:01G, C*05
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.
RYPLTFGW, restricted by A*2402, 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 61180

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
		Show epitope variants
Epitope Name	RW8
Subtype	B
Species (MHC/HLA)	human(A*24:02)
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.
Nef epitope RYPLTFGW, RW8_134-141,-specific T cells were less cytotoxic to variants than autologous RW8 in acute infection. No variants tested cross-reacted with T cells specific to autologous RW8.

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 61235

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef
Epitope	`RYPLTFGW`	Epitope Alignment
		Show epitope variants
Epitope Name	RW8
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, immunodominance, TCR usage, variant cross-reactivity

Notes

Recent findings of the HIV-specific TCR repertoire are reviewed here. Epitope RW8, RYPLTFGW, is superimposed within RF10, RYPLTFGWCF, and both drive distinct HIV-specific CTL repertoires exhibiting different properties. RW8-CTL avidity correlates with ability of infected individuals to respond to antigen with sensitivity, polyfunctionality and viral suppression.

References

Lissina2016 Anna Lissina, Lisa A. Chakrabarti, Masafumi Takiguchi, and Victor Appay. TCR Clonotypes: Molecular Determinants of T-Cell Efficacy against HIV. Curr. Opin. Virol., 16:77-85, Feb 2016. PubMed ID: 26874617. Show all entries for this paper.

Displaying record number 61248

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
		Show epitope variants
Epitope Name	RW8
Subtype	B
Species (MHC/HLA)	human(A*24:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	KI-060: A24:02, A26:01, B40:02, B52:01, C03:04, C12:02; KI-071: A24:02, A31:01, B40:06, B52:01; KI-069: A24:02, B40:06, B52:01, C03:04, C12:02; KI-087: A24:02, B40:01, B55:02, C01:02, C03:04; KI-708: A24:02, A31:01, B07:02, B15:01, C03:03, C07:02; KI-130: A24:02, B07:02, B52:01, C07:02, C12:02; KI-092: A02:06, A24:02, B48:01, B51:01, C08:01, C14:02; KI-102: A02:06, A24:02, B07:02, B35:01, C03:03, C07:02; KI-158: A24:02, A33:03, B44:03, B52:01, C12:02, C14:03; KI-161: A24:02, A26:01, B35:01, B54:01, C01:02, C*03:03
Country	Japan
Experimental methods	Chromium-release assay, Other, Relative replication capacity assay, Tetramer binding
Keywords	escape, structure, variant cross-reactivity

Notes

Two different immune repercussions are noted as a result of a single Y135F amino acid substitution that lies within 2 superimposed epitopes, RF10 (RYPLTFGWCF) and RW8 (RYPLTFGW). First, Y135F induces a new CTL population to recognize escape epitope RF10-2F, RfPLTFGWCF, but no new CTL population is induced by the escape RW8-2F, RfPLTFGW.
RW8-specific CTL cross recognize both WT and 2F forms of RW8, while RF10-specific clones show stronger specificity for WT epitope than the 2F mutant.
Second, crystal structures of HLA-A*2402-RW8-2F and HLA-A*2402-RF1-2F were compared with non-mutant complexes. A major hydrogen-bonding difference was loss of contact between P2 and the A*2402 H70. Water molecule distribution was not greatly changed in the RW8-A*2402 complex, however RF10-A*2402 complex went from 6 water-molecule-mediated-H-bonds to 8 for the RF10-2F mutant, affecting stability of peptide-MHC binding.
3/15 HLA-A*2402+, ART-naive HIV-1 infected patients did not carry RW8 mutants.

References

Sun2016 Xiaoming Sun, Yi Shi, Tomohiro Akahoshi, Mamoru Fujiwara, Hiroyuki Gatanaga, Christian Schönbach, Nozomi Kuse, Victor Appay, George F. Gao, Shinichi Oka, and Masafumi Takiguchi. Effects of a Single Escape Mutation on T Cell and HIV-1 Co-Adaptation. Cell Rep., 15(10):2279-2291, 7 Jun 2016. PubMed ID: 27239036. Show all entries for this paper.

Displaying record number 61669

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
		Show epitope variants
Epitope Name	RW8
Species (MHC/HLA)	human(A*24:02)
Immunogen	peptide-HLA interaction
Experimental methods	Other, Tetramer binding
Keywords	structure, NK cells, protective allele

Notes

A structure-driven approach to characterize specific peptide preferences of protective HLA-B*5701-restricted epitopes of HIV-1 with NK cell receptors is used in this study. In addition, HLA-Bw4-restricted epitope ligands recognized by KIR3DS1 were identified, showing direct interaction between these molecules resulting in NK cell activation.
C-terminal epitope residues are known to affect KIR3DL1 recognition so that replacing position 8 of the human peptide LF9, LSSPVTKSF, with glutamate (E) i.e. LSSPVTKeF dramatically reduces binding and this is possibly due to side chain protrusion of E that would clash with E282 of the KIR D2 domain. And replacing that position with alanine (A) might disallow contact with L166 of the KIR D1 domain, abolishing peptide-KIR3DL1*001 interaction.
Allotype-specific differences were seen in binding to KIR3DS1 as compared to KIR3DL1, specifically at amino acids W138, S163, R166 and L199 (not found in KIR3DL1). W138, S163, R166 strongly inhibit binding of KIR3DL1*001 to HLA-A*2402; but only R166 impairs binding of KIR3DL1*001 to HLA-B*5701.
Peptide-specific effects also modulate binding sensitivity of KIR3DS1-like mutants. HIV-Nef RW8, RYPLTFGW, presented by HLA-A*2402 is bound by KIR3DL1*001 as well as its mutant L199 form. The variant peptide RW8 Y2F however (and not the variant peptide RW8 W8A), has appreciable loss of binding to the L199 form of KIR3Dl1*001.

References

OConnor2015 Geraldine M. O'Connor, Julian P. Vivian, Emma Gostick, Phillip Pymm, Bernard A. P. Lafont, David A. Price, Jamie Rossjohn, Andrew G. Brooks, and Daniel W. McVicar. Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1. J. Virol., 89(10):5213-5221, May 2015. PubMed ID: 25740999. Show all entries for this paper.

Displaying record number 60238

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Species (MHC/HLA)	human(A*29)
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.
RYPLTFGW had a significantly positive association with HLA A*29; it was recognized by 3/19 A*29-positive subjects and 2/175 A*29-negative subjects.

References

Displaying record number 52629

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A33)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, A33, B14, B35, C04:01, C08:02
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	binding affinity, acute/early infection, early-expressed proteins

Notes

All proteins were scanned and optimal epitopes were mapped in a study of CD8+ IFNγ T-cell responses in 21 men within 15-92 days post-HIV-1 infection. Subjects initially showed a narrow immune response with a mean of 2.3 epitopes recognized per patient. The immune response broadened later in infection. No correlation between the plasma viral load and the number of recognized epitopes or the frequency of IFNγ-secreting cells was observed, and there was no correlation between the functional avidity of a response and the abundance of IFNγ-secreting cells that recognized the epitope. The first epitopes to be recognized did not tend to be the most avid, and earliest responses tended to be directed against Nef, Tat, Vpr, and Env.
All HIV-1 proteins except Vpu were recognized, and responses to a total of 41 optimal epitopes were characterized; 24 had been identified previously. 48% of the total T-cell responses were directed against Nef and 43% were directed against Gag.
More common HLA alleles were less frequently used in primary infection than less common alleles, for example A3, B35, B57, and B62 were more frequently utilized than A1, A2, A30, and A44.

References

Cao2003 Jianhong Cao, John McNevin, Sarah Holte, Lisa Fink, Lawrence Corey, and M. Juliana McElrath. Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8+ T Cells in Primary HIV-1 Infection. J. Virol., 77(12):6867-6878, Jun 2003. PubMed ID: 12768006. Show all entries for this paper.

Displaying record number 60237

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Species (MHC/HLA)	human(B*18)
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.
RYPLTFGW had a significantly positive association with HLA B*18; it was recognized by 8/17 B*18-positive subjects and 16/226 B*18-negative subjects.

References

Displaying record number 60240

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Species (MHC/HLA)	human(B*27)
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.
RYPLTFGW had a significantly positive association with HLA B*27; it was recognized by 2/22 B*27-positive subjects and 0/153 B*27-negative subjects.

References

Displaying record number 55619

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Subtype	B
Species (MHC/HLA)	human(B27)
Immunogen	HIV-1 infection
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction

Notes

Peptide prediction programs based on MHC binding, proteasomal cleavage and TAP transport were applied to select novel epitopes absent from the Los Alamos HIV database. 22 novel epitopes were tested by IFN-gamma ELISpot and 19 (11 HLA-B27 restricted, 8 HLA-B57 restricted) induced strong positive responses.
Magnitude of response generated was similar to that of previously identified epitopes, but the number of individuals responding was lower. This could be explained by less stringent HLA-typing of subjects and perhaps high sequence variability within these novel epitopes.
RW8, RYPLTFGW, is a known HLA-B27-restricted epitope used as a positive control for eliciting CTL IFN-gamma response.

References

Schellens2008 Ingrid M. M. Schellens, Can Kesmir, Frank Miedema, Debbie van Baarle, and José A. M. Borghans. An Unanticipated Lack of Consensus Cytotoxic T Lymphocyte Epitopes in HIV-1 Databases: The Contribution of Prediction Programs. AIDS, 22(1):33-37, 2 Jan 2008. PubMed ID: 18090389. Show all entries for this paper.

Displaying record number 1064

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141 LAI)
Epitope	`RYPLTFGW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B27)
Immunogen
Experimental methods
Keywords

Notes

Optimal peptide defined by titration.

References

CulmannPerCom B. Culmann. Personal communication, 1998. Show all entries for this paper.

Displaying record number 60239

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Species (MHC/HLA)	human(B35:02, B35:03, B*53:01)
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.
RYPLTFGW had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 2/5 B*3502,B*3503,B*5301-positive subjects and 5/194 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 60234

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HXB2 Location	Nef(134-141) DNA(9196..9219)	Nef Epitope Map
Author Location	Nef(134-141)
Epitope	`RYPLTFGW`	Epitope Alignment
Epitope Name	RW8
Species (MHC/HLA)	human(C*04)
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.
RYPLTFGW had a significantly positive association with HLA C*04; it was recognized by 39/81 C*04-positive subjects and 34/260 C*04-negative subjects.