Search CTL/CD8+ T-Cell Epitope Database

Found 19 matching records:

Displaying record number 59515

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	Env(31-39)
Epitope	`AENLWVTVY`	Epitope Alignment
Epitope Name	AY9
Species (MHC/HLA)	human(B*15:17)
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.
AENLWVTVY had a significantly positive association with HLA B*1517; it was recognized by 1/2 B*1517-positive subjects and 5/273 B*1517-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 59514

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	Env(31-39)
Epitope	`AENLWVTVY`	Epitope Alignment
Epitope Name	AY9
Species (MHC/HLA)	human(B*15:40)
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.
AENLWVTVY had a significantly positive association with HLA B*1540; it was recognized by 1/1 B*1540-positive subjects and 6/275 B*1540-negative subjects.

References

Displaying record number 59512

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	Env(31-39)
Epitope	`AENLWVTVY`	Epitope Alignment
Epitope Name	AY9
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.
AENLWVTVY had a significantly positive association with HLA B*18; it was recognized by 8/23 B*18-positive subjects and 13/318 B*18-negative subjects.

References

Displaying record number 54101

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location
Epitope	`AENLWVTVY`	Epitope Alignment
Epitope Name	AY9
Species (MHC/HLA)	human(B*18:01)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*1801 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 54160

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp120(31-39 HIV-MN)
Epitope	`AENLWVTVY`	Epitope Alignment
		Show epitope variants
Epitope Name	AY9
Subtype	B
Species (MHC/HLA)	human(B*18:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	PIC1362: A02:01, A25:01, B18:01, B51:01, C01:02, C12:03
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, mutation acquisition, optimal epitope

Notes

T-cell immunity and the impact of selection were longitudinally studied in a patient from the time of transmission. New epitopes were detected at sites that were shown to be under positive selection. Env was found to be the major target of CTLs and most of the new epitopes were found here. One third of the sites examined were associated with epitope escape mutations from CTL. Acquisition of mutations found at high frequency in the database was suggested to be a result of reversion of CTL epitopes in the absence of immune targeting.
This is a newly defined epitope. Position 1 in the epitope had potentially experienced positive selection. AdNLWVTVY, tdNLWVTVY, tEdLWVTVY, eEdLWVTVY and AEdsWVTVY escape variants were found.

References

Liu2006 Yi Liu, John McNevin, Jianhong Cao, Hong Zhao, Indira Genowati, Kim Wong, Sherry McLaughlin, Matthew D. McSweyn, Kurt Diem, Claire E. Stevens, Janine Maenza, Hongxia He, David C. Nickle, Daniel Shriner, Sarah E. Holte, Ann C. Collier, Lawrence Corey, M. Juliana McElrath, and James I. Mullins. Selection on the Human Immunodeficiency Virus Type 1 Proteome following Primary Infection. J. Virol., 80(19):9519-9529, Oct 2006. PubMed ID: 16973556. Show all entries for this paper.

Displaying record number 58157

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp120(31-39)
Epitope	`AENLWVTVY`	Epitope Alignment
		Show epitope variants
Epitope Name	AY9
Subtype	B
Species (MHC/HLA)	human(B*18:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	PIC1362: A02:01, A25:01, B18:01, B51:01, C01:02, C12:03
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, acute/early infection

Notes

CTL responses were studied in a drug-naive patient for 4 years, beginning at the time of infection. CTL recognition of 25 epitopes was observed, and 18 of them underwent mutational changes, usually indicative of escape.
Evolving epitope AENLWVTVY underwent weak selection during 4 years of infection.
Variant AdNLWVTVY arose by 400 days post-infection, and was replaced by AEdsWVTVY after 800 days post-infection. The latter variant was associated with loss of EliSpot response to the epitope.

References

Liu2011a Yi Liu, John P. McNevin, Sarah Holte, M. Juliana McElrath, and James I. Mullins. Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection. PLoS One, 6(1):e15639, 2011. PubMed ID: 21283794. Show all entries for this paper.

Displaying record number 59090

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp120(31-39)
Epitope	`AENLWVTVY`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B*18:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	PIC1362: A02:01, A25:01, B18:01, B51:01, C01:02, C12:03
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	viral fitness and reversion

Notes

CTL responses were studied in a single drug-naive individual during the first 4 years of infection. 25 CTL epitopes were identified; 17 of them underwent evolution; 15 mutant forms that escaped or partially escaped were detected.
AENLWVTVY was an epitope whose frequency decreased during 4 years of infection; 3 escape mutants were detected (TEdLWVTVY, eEDLWVTVY, aEdsWVTVY).

References

Liu2007a Yi Liu, John McNevin, Hong Zhao, Denis M. Tebit, Ryan M. Troyer, Matthew McSweyn, Ananta K. Ghosh, Daniel Shriner, Eric J. Arts, M. Juliana McElrath, and James I. Mullins. Evolution of Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitopes: Fitness-Balanced Escape. J. Virol., 81(22):12179-12188, Nov 2007. PubMed ID: 17728222. Show all entries for this paper.

Displaying record number 54105

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location
Epitope	`AENLWVTVY`	Epitope Alignment
Epitope Name	AY9
Species (MHC/HLA)	human(B*44)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*44 epitope.

References

Displaying record number 1808

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp120(30-38)
Epitope	`AENLWVTVY`	Epitope Alignment
Species (MHC/HLA)	human(B*44)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, acute/early infection

Notes

The CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A*02, A*03, and B*07 was studied in eight HIV-1-infected subjects, two with acute infection, five with chronic, and one long-term non-progressor (LTNP).
2 to 17 epitopes were recognized in a given individual, A*02-restricted CTL response tended to be narrow and never dominated the response. 25/27 epitopes were targeted by at least one person.
AENLWVTVY was one of the B*44-restricted epitopes tested for responses in this investigation.

References

Day2001 C. L. Day, A. K. Shea, M. A. Altfeld, D. P. Olson, S. P. Buchbinder, F. M. Hecht, E. S. Rosenberg, B. D. Walker, and S. A. Kalams. Relative dominance of epitope-specific cytotoxic T-lymphocyte responses in human immunodeficiency virus type 1-infected persons with shared HLA alleles. J. Virol., 75(14):6279-91, Jul 2001. URL: http://jvi.asm.org/cgi/content/full/75/14/6279. PubMed ID: 11413294. Show all entries for this paper.

Displaying record number 622

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp160(30-39 WEAU)
Epitope	`AENLWVTVY`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B44)
Immunogen	HIV-1 infection
Experimental methods
Keywords	immunodominance, escape

Notes

Two CTL lines from the patient WEAU were studied -- one had an optimal peptide of (A)AENLWVTVYY, and the other (A)AENLWVTVY, and both responded equally well with one or two N-term Alanines.
Rapidly post-infection, a strong immunodominant response was observed against this epitope.
The naturally occurring forms of the peptide found in WEAU were tested as targets for early WEAU CTLs -- the form TENLWVTVY was as reactive as the wild type AENLWVTVY -- but the forms AKNLWVTVY, AGNLWVTVY, AANLWVTVY did not serve as targets.
The glutamic acid in the second position is a B44 anchor residue.
Goulder1997e and Borrow1998 are reviews of immune escape that summarizes this study in the context of CTL escape to fixation.

References

Borrow1997 P. Borrow, H. Lewicki, X. Wei, M. S. Horwitz, N. Peffer, H. Meyers, J. A. Nelson, J. E. Gairin, B. H. Hahn, M. B. Oldstone, and G. M. Shaw. Anti-Viral Pressure Exerted by HIV-1-Specific Cytotoxic T Lymphocytes (CTLs) During Primary Infection Demonstrated by Rapid Selection of CTL Escape Virus. Nat. Med., 3:205-211, 1997. Genetic pathways of virus escape from CTL pressure resembled virus escape from antiretroviral therapy. PubMed ID: 9018240. Show all entries for this paper.

Borrow1998 P. Borrow and G. M. Shaw. Cytotoxic T-Lymphocyte Escape Viral Variants: How Important Are They in Viral Evasion of Immune Clearance In Vivo? Immunol. Rev., 164:37-51, 1998. PubMed ID: 9795762. Show all entries for this paper.

Goulder1997e P. Goulder, D. Price, M. Nowak, S. Rowland-Jones, R. Phillips, and A. McMichael. Co-Evolution of Human Immunodeficiency Virus and Cytotoxic T-Lymphocyte Responses. Immunol. Rev., 159:17-29, 1997. PubMed ID: 9416500. Show all entries for this paper.

Displaying record number 1557

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp120(30-38 SF2)
Epitope	`AENLWVTVY`	Epitope Alignment
Species (MHC/HLA)	human(B44)
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-B44+ individuals that had a CTL response to this epitope broken down by group: 1/8 group 1, 2/3 group 2, and 3/4 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 52112

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp120
Epitope	`AENLWVTVY`	Epitope Alignment
Species (MHC/HLA)	human(B44)
Immunogen	HIV-1 infection
Experimental methods
Keywords	epitope processing

Notes

AC2 is a B44 restricted CTL clone that recognizes AENLWVTVY.
CTL could be activated by a fusion protein of an HIV protein and anthrax lethal factor (LFn-HIV) that promotes antigen presenting cell uptake of exogenous protein and allows processing through the MHC class I pathway. This strategy for CTL detection could allow antigen presentation without generation of cells by the standard methods of using live viral vectors carrying a protein, or by loading the cells with peptides and by-passing processing.

References

Cao2002 Huyen Cao, Deepak Agrawal, Nicholas Kushner, Neal Touzjian, Max Essex, and Yichen Lu. Delivery of exogenous protein antigens to major histocompatibility complex class I pathway in cytosol. J. Infect. Dis., 185(2):244-251, 15 Jan 2002. PubMed ID: 11807699. Show all entries for this paper.

Displaying record number 53362

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	( B consensus)
Epitope	`AENLWVTVY`	Epitope Alignment
Epitope Name	AY9
Subtype	B
Species (MHC/HLA)	human(B44)
Immunogen	HIV-1 infection
Patient MHC/HLA	A11, A29, B44, B8, Cw4, Cw7
Country	United States
Experimental methods	Chromium-release assay, Cytokine production, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	assay or method development, memory cells, characterizing CD8+ T cells

Notes

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

References

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

Displaying record number 55042

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location
Epitope	`AENLWVTVY`	Epitope Alignment
Species (MHC/HLA)	human(B44)
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 AENLWVTVY elicited a magnitude of response of 160 SFC with a functional avidity of 5nM.

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 56044

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp120
Epitope	`AENLWVTVY`	Epitope Alignment
Epitope Name	AY9(gp120)
Subtype	B
Species (MHC/HLA)	human(B44)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	chronic infection

Notes

49 ART-naive chronically HIV-1 infected Chinese subjects' CTLs were tested with 413 OLPs in IFN-γ 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.
Previously described HLA-B44-restricted epitope AENLWVTVY elicited an immune response in Chinese HIV-1 positive subjects as part of peptides LGMLMICSAAENLWVTVY and AAENLWVTVYYGVPVWK.
1 of the 6 HLA-B44 carriers responded to AENLWVTVY-containing peptide, AAENLWVTVYYGVPVWK, with average magnitude of CTL response of 620 SFC/million PBMC (author communication and Fig.1).

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 57436

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp160
Epitope	`AENLWVTVY`	Epitope Alignment
		Show epitope variants
Epitope Name	AY9
Subtype	B
Species (MHC/HLA)	human(B*44:03)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Chromium-release assay
Keywords	escape, acute/early infection

Notes

3 subjects with acute HIV infection were studied longitudinally by 454-ultra deep-sequencing of 4 HIV-1 epitope regions that have early recognition and escape. Over 50 variant forms of each CTL epitope targeted during the first 3-6 weeks of infection were found, i.e. 7-25 times more than variation in the control V3 region of Env, at earlier times. In very early infection, reversions were seen where immune pressure was considerable but they were absent outside epitopes. A strong case was made for establishment of infection via a single virus.
All 3 subjects' epitopes have been tested in previous publications.
AY9 from patient WEAU spawns 2 escape lineages: AEkLWVTVY and tENLWVTVY. Non-synonymous mutations were enriched significantly by day 10 postinfection, and selection was estimated to have begun on day 5. This transmitted epitope is dominant until the last 454 ultra-deep sequencing sample point, however it diminished from 86.21% at day 20 to 37.72% at day 30. It was undetectable from day 136 onwards using conventional sequencing. AY9 had an accumulation/loss rate of -0.24.

References

Fischer2010 Will Fischer, Vitaly V. Ganusov, Elena E. Giorgi, Peter T. Hraber, Brandon F. Keele, Thomas Leitner, Cliff S. Han, Cheryl D. Gleasner, Lance Green, Chien-Chi Lo, Ambarish Nag, Timothy C. Wallstrom, Shuyi Wang, Andrew J. McMichael, Barton F. Haynes, Beatrice H. Hahn, Alan S. Perelson, Persephone Borrow, George M. Shaw, Tanmoy Bhattacharya, and Bette T. Korber. Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing. PLoS One, 5(8):e12303, 2010. PubMed ID: 20808830. Show all entries for this paper.

Displaying record number 53226

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp160(30-38 WEAU)
Epitope	`AENLWVTVY`	Epitope Alignment
		Show epitope variants
Epitope Name	gp160 AY9
Subtype	B
Species (MHC/HLA)	human(B*44:03)
Immunogen	HIV-1 infection
Patient MHC/HLA	WEAU: A01, A29, B08, B44
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	dynamics, immunodominance, escape, acute/early infection, kinetics, autologous responses, optimal epitope

Notes

Primary CD8+ T-cell response to Env, Tat and Gag and the extent, kinetics and mechanisms of viral escape were examined in three patients. Rapid escape, within weeks from infection, from HIV specific CTL responses was observed in all three patients, but the kinetics and extent of the escape differed depending on the breadth and co-dominant distribution of CTL-mediated pressure. The two patients that rapidly declined had more focused immunodominant responses, while the single patient that had low viral load and stable CD4 counts for seven years had a broad co-dominant response and less escape.
The patient WEAU had high viral loads and rapid CD4 decline. WEAU mounted 14 detected CTL responses, with distinct patterns of immunodominance. WEAU did not control viral replication well, and escape mutations occurred early and 4/14 had changes that could have resulted in escape, and two were confirmed as escape.
This was the immunodominant response in acute infection in WEAU, and there was rapid escape in the epitope AENLWVTVY, with three variants observed by day 30 from the onset of symptoms. Additional mutations continued to develop, so that there were 9 different forms observed through the course of sampling. The variants all conferred different levels of reduction in CTL response, double mutations or anchor mutations tended to cause the greatest reduction: AaNLWVTaY, tNkWVTVY, AgNLWVTVY, AkNLWVTVY, although the double mutant tENLWVTiY elicted a very strong CTL response, suggesting it might not be an escape form.
Dynamics of this response are shown in Fig. S2 of Yang2019 which developed mathematical models with data from Jones2004. Yang2019 concluded that, in general, relative CTL response breadth increased moderately during the first symptomatic month and then remained relatively stable through the first 400 days post-infection. Analysis also suggested slow expansion kinetics for most HIV-specific CTL responses and the presence of intra- and interclonal competition.
Patient WEAU autologous epitope AENLWVTVY nearly entirely overlaps with patient SUMA autologous epitope ENLWVTVYY which was also studied in this paper.

References

Jones2004 Nicola A. Jones, Xiping Wei, Darren R. Flower, MaiLee Wong, Franziska Michor, Michael S. Saag, Beatrice H. Hahn, Martin A. Nowak, George M. Shaw, and Persephone Borrow. Determinants of Human Immunodeficiency Virus Type 1 Escape from the Primary CD8+ Cytotoxic T Lymphocyte Response. J. Exp. Med., 200(10):1243-1256, 15 Nov 2004. PubMed ID: 15545352. Show all entries for this paper.

Yang2019 Yiding Yang, and Vitaly V. Ganusov. Defining Kinetic Properties of HIV-Specific CD8(+) T-Cell Responses in Acute Infection. Microorganisms, 7(3):microorganisms7030069 doi, Mar 2019. PubMed ID: 30836625 Show all entries for this paper.

Displaying record number 59513

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	Env(31-39)
Epitope	`AENLWVTVY`	Epitope Alignment
Epitope Name	AY9
Species (MHC/HLA)	human(C*02)
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.
AENLWVTVY had a significantly positive association with HLA C*02; it was recognized by 6/42 C*02-positive subjects and 7/276 C*02-negative subjects.

References

Displaying record number 54677

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HXB2 Location	gp160(31-39) gp120(31-39) DNA(6315..6341)	gp160 Epitope Map
Author Location	gp160(31-39)
Epitope	`AENLWVTVY`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A29, B44, B8
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	HAART, ART, escape, viral fitness and reversion

Notes

In order to reconcile apparent conflicts between a CTL-protective role as suggested by HLA-1 alleles associated with different rates of progression to AIDS, and a CTL non-protective role as suggested by the fact that virus clearance following ART is not impaired in advanced AIDS, a model is made that quantifies the efficiency of HIV-1-specific CTLs in vivo. As a surrogate for the actual rate of CTL-killing of infected cells, the model rests on calculating virus escape rate for an epitope and subtracting its reversion rate upon transmission to a non-restricting HLA bearing host. It is shown that CTLs recognizing a single epitope kill only 2% of productively infected CD4+ cells. The rate of CTL lysis was found to be significantly faster during primary infection than in chronic infection. However, the authors suggest that small differences in CTL lysis rate can translate into large differences in terms of absolute numbers of infected cells killed, which are likely to be clinically relevant.
The best estimate of escape rate for this epitope, AENLWVTVY, was found to be 0.048/day (upper bound on rate of escape = 0.053), with SE of 0.022.
Mutations at position 30 (E30G and E30A) were shown to confer escape.

References

Asquith2006 Becca Asquith, Charles T. T. Edwards, Marc Lipsitch, and Angela R. McLean. Inefficient Cytotoxic T Lymphocyte-Mediated Killing of HIV-1-Infected Cells In Vivo. PLoS Biol., 4(4):e90, Apr 2006. PubMed ID: 16515366. Show all entries for this paper.