Search CTL/CD8+ T-Cell Epitope Database

Found 24 matching records:

Displaying record number 59798

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
Species (MHC/HLA)	human(A*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.
IEIKDTKEAL had a significantly positive association with HLA A*01; it was recognized by 3/44 A*01-positive subjects and 1/188 A*01-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 59800

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
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.
IEIKDTKEAL had a significantly positive association with HLA A*29; it was recognized by 3/27 A*29-positive subjects and 4/232 A*29-negative subjects.

References

Displaying record number 59795

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
Species (MHC/HLA)	human(B*08)
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.
IEIKDTKEAL had a significantly positive association with HLA B*08; it was recognized by 11/23 B*08-positive subjects and 14/281 B*08-negative subjects.

References

Displaying record number 59796

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
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.
IEIKDTKEAL had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 15/37 B*3502,B*3503,B*5301-positive subjects and 25/304 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 56362

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL9
Subtype	B
Species (MHC/HLA)	human(B*40)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	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-B*40-associated substitution within optimally defined epitope IEIKDTKEAL is at positions E2, IeIKDTKEAL.

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 59797

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
Species (MHC/HLA)	human(B*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.
IEIKDTKEAL had a significantly positive association with HLA B*40; it was recognized by 7/22 B*40-positive subjects and 7/259 B*40-negative subjects.

References

Displaying record number 54889

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location
Epitope	`IEIKDTKEAL`	Epitope Alignment
Species (MHC/HLA)	human(B40)
Immunogen	HIV-1 infection, vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	vaccine-induced immune responses, characterizing CD8+ T cells

Vaccine Details

Vaccine type	canarypox, canarypox prime with recombinant protein boost
Vaccine strain	B clade BRU, B clade LAI, B clade MN, multiple epitope immunogen
Vaccine component	Gag, gp120, gp41, Nef, Pol, Protease

Notes

CD8+ T-cell function induced by HIV-1 immunogens and natural infection was compared. Natural infections consisted of early, chronic, and long term nonprogressors.
B27- and B57-restricted CD8+ T cells from nonprogressors exhibited greater expansion than those restricted by other alleles, providing an explanation for the observed association between HLA-B27/B57 and control of HIV-1 infection.

References

Horton2006 Helen Horton, Ian Frank, Ruth Baydo, Emilie Jalbert, Justin Penn, Sean Wilson, John P. McNevin, Matthew D. McSweyn, Deborah Lee, Yunda Huang, Stephen C. De Rosa, and M. Juliana McElrath. Preservation of T Cell Proliferation Restricted by Protective HLA Alleles Is Critical for Immune Control of HIV-1 Infection. J. Immunol., 177(10):7406-7415, 15 Nov 2006. PubMed ID: 17082660. Show all entries for this paper.

Displaying record number 55714

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10-B40
Subtype	B, F
Species (MHC/HLA)	human(B40)
Immunogen	HIV-1 infection
Country	Argentina
Experimental methods
Keywords	dynamics, HLA associated polymorphism

Notes

Dynamics of CTL escape mutations was studied theoretically by analyzing plasma samples from 302 subjects (collected over 20 years). HLA associated polymorphisms accumulated in a subtype-specific manner.
Epitope IEIKDTKEAL with anchor residues at I(E)IKDTKEAL mutates to variant IEIrDTKEAL. The consensus epitope IEIkDTKEAL and a polymorphism IEIkDTKEAL increases over time.

References

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

Displaying record number 56029

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10(p17)
Subtype	B
Species (MHC/HLA)	human(B40)
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-B40-restricted epitope IEIKDTKEAL elicited an immune response in Chinese HIV-1 positive subjects as part of peptides LYCVHQRIEIKDTKEAL and IEIKDTKEALEKIEEEQNK.
3 of the 20 HLA-B40 carriers responded to a IEIKDTKEAL-containing peptide with average magnitude of CTL response of 363 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 54364

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	B40-IL10(p17)
Species (MHC/HLA)	human(B40)
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 60955

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*40:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	51729: A24:02, A24:02, B35:05, B40:01, C03:04, C04:01
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.
IEIKDTKEAL, restricted by B*4001, 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 116

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Species (MHC/HLA)	human(B*40:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*4001 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 59799

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
Species (MHC/HLA)	human(B*42:01)
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.
IEIKDTKEAL had a significantly positive association with HLA B*4201; it was recognized by 1/5 B*4201-positive subjects and 0/183 B*4201-negative subjects.

References

Displaying record number 1809

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Species (MHC/HLA)	human(B60, B61)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

No immunodominant responses were detected to five B*61-restricted epitopes tested.
All five B*60-restricted epitopes were reactive in another subject, and the B*60-restricted responses together contributed over one-third of the total CTL response.

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 62935

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HXB2 Location	Gag(92-101) p17(92-101)	Gag Epitope Map
Author Location	Gag(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B60)
Immunogen	engineered, virus
Experimental methods	CTL suppression of replication
Keywords	epitope processing, viral replication, Nef-mediated down-regulation

Notes

Nef impaired HIV-specific CTL-mediated suppression of HIV replication but this effect was ablated in IIIB-infected target T2 T cells (which are unable to present Ag on MHC Class I molecules) and with engineered CTL cell line T3F3 (which directly interacts with gp120 independent of Ag processing). Vpr did not impair CTL-mediated viral suppression.
B60-restricted IEIKDTKEAL-specific CTL clone 161JD27 suppressed viral replication in IIIB-infected T1 cells, but not in T2 cells (which are unable to present Ag on MHC Class I molecules).

References

Yang2002b Otto O. Yang, Phuong Thi Nguyen, Spyros A. Kalams, Tanya Dorfman, Heinrich G. Gottlinger, Sheila Stewart, Irvin S. Y. Chen, Steven Threlkeld, and Bruce D. Walker. Nef-mediated resistance of human immunodeficiency virus type 1 to antiviral cytotoxic T lymphocytes. J Virol, 76(4):1626-31 doi, Feb 2002. PubMed ID: 11799157 Show all entries for this paper.

Displaying record number 1522

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101 SF2)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Species (MHC/HLA)	human(B60)
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-B60+ individuals that had a CTL response to this epitope broken down by group: 0/2 group 1, 1/1 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 1840

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17( SF2)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

This epitope was mapped by ELISPOT in a study identifying new HLA-B60 epitopes.
B60 is present in 10-20% of the Caucasoid and very common in Asian populations.

References

Altfeld2000 M. A. Altfeld, A. Trocha, R. L. Eldridge, E. S. Rosenberg, M. N. Phillips, M. M. Addo, R. P. Sekaly, S. A. Kalams, S. A. Burchett, K. McIntosh, B. D. Walker, and P. J. Goulder. Identification of dominant optimal HLA-B60- and HLA-B61-restricted cytotoxic T-lymphocyte (CTL) epitopes: rapid characterization of CTL responses by enzyme-linked immunospot assay. J. Virol., 74:8541, 2000. PubMed ID: 10954555. Show all entries for this paper.

Displaying record number 52239

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods
Keywords	class I down-regulation by Nef

Notes

Nef down-modulates class I protein expression, and this study demonstrates directly that Nef-deleted HIV-1 NL-43 can be more effectively killed in vitro than NL-43 with an intact Nef. The effect was shown to be specific for class I presentation of epitopes, and unlike Nef, deleting Vpr did not alter CTL susceptibility of NL43 infected cells. The CTL clone 161JD27, specific for the class I B60 presented epitope IEIKDTKEAL, was one of four used in this study.

References

Yang2002 Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429. Show all entries for this paper.

Displaying record number 52788

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101 NL43)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
Subtype	B
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods	CTL suppression of replication, Chromium-release assay
Keywords	escape

Notes

Virus was cultured in the presence of CTL lines specific for 5 different epitopes (SLYNTVATL, ILKEPVHGV, IEIKDTKEAL, SEGATPQDL, and KEKGGLEGL) to study the emergence of escape mutations. Escape varied between clones for the same epitope, and between different epitopes. Gag and RT epitope escape, if it occurred at all, tended to be monoclonal and within the epitope, indicating strong fitness constraints, while the Nef epitope escape was rapid, polyconal, and sometimes the result of upstream frameshifts.
There was one cloned cell line that recognized IEIKDTKEAL, 161JD27. After 2 weeks of passaging HIV-1 in the presence of 161JD27, no mutations were observed within the epitope in 10 sequences; one of the 10 had a single E -> K substitution 6 amino acids beyond the C-terminal end of the epitope.

References

Yang2003 Otto O Yang, Phuong Thi Nguyen Sarkis, Ayub Ali, Jason D Harlow, Christian Brander, Spyros A Kalams, and Bruce D Walker. Determinant of HIV-1 Mutational Escape from Cytotoxic T Lymphocytes. J. Exp. Med., 197(10):1365-1375, May 2003. PubMed ID: 12743169. Show all entries for this paper.

Displaying record number 52852

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	Gag(92-101 B consensus)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
Subtype	B
Species (MHC/HLA)	human(B60)
Immunogen	vaccine
Experimental methods	Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	dynamics, escape, mutation acquisition

Vaccine Details

Vaccine type	adeno-associated virus (AAV)
Vaccine component	gp120

Notes

HIV-1 gp120 is shown to suppress the ability of antigen-specific CTLs to migrate or remain at sites of high viral replication by concentration-dependent chemotaxis and fugetaxis. Directional T-cell movement is shown to depend on the interaction of the V2 and V3 loops with the CXCR4 receptor. X4 HIV-1 gp120 causes the migration of T-cells, including HIV-1 specific CTL, away from infected target cells, another potential mechanism for immune evasion.

References

Brainard2004 Diana M. Brainard, William G. Tharp, Elva Granado, Nicholas Miller, Alicja K. Trocha, Xiang-Hui Ren, Brian Conrad, Ernest F. Terwilliger, Richard Wyatt, Bruce D. Walker, and Mark C. Poznansky. Migration of Antigen-Specific T Cells away from CXCR4-Binding Human Immunodeficiency Virus Type 1 gp120. J. Virol., 78(10):5184-5193, May 2004. PubMed ID: 15113900. Show all entries for this paper.

Displaying record number 53149

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	Gag/p17-IL10
Subtype	B
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods	Chromium-release assay
Keywords	binding affinity, epitope processing, TCR usage, characterizing CD8+ T cells

Notes

Killing efficiency of CTLs and their ability to suppress viral replication is shown to depend more on epitope specificity than to antigenic avidity. Different clones recognizing the same epitope had similar killing efficiency despite their variation in avidity. Nef specific CTL clones tended to be most inhibitory, followed by Gag, then by RT specific clones, regardless of avidity.
1/14 CTL T-cell clones tested were specific for Gag/p17-IL10. Under conditions of excess peptide (100ug/ml), there was no difference in their lytic potential; all possessed similar effector capacity. Avidity was measured as the sensitizing dose of peptide required for 50% of maximal killing (SD50), which varied from 20 pg/ml to 100 ng/ml, over four orders of magnitude for all 14 epitopes. The SD50 value for the Gag/p17-IL10 clone was 8,000 pg/ml.

References

Yang2003a Otto O. Yang, Phuong T. Nguyen Sarkis, Alicja Trocha, Spyros A. Kalams, R. Paul Johnson, and Bruce D. Walker. Impacts of Avidity and Specificity on the Antiviral Efficiency of HIV-1-Specific CTL. J. Immunol., 171(7):3718-3724, 1 Oct 2003. PubMed ID: 14500671. Show all entries for this paper.

Displaying record number 115

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17
Epitope	`IEIKDTKEAL`	Epitope Alignment
Species (MHC/HLA)	human(B60)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

CTL specific for HIV epitopes were used to show that the mediators of both the cytolytic (granzyme A was used as the marker) and non-cytolytic (HIV-1 inhibitory chemokines MIP-1 α and RANTES were used as markers) anti-viral responses are localized within the CTL's cytotoxic granules.

References

Wagner1998b L. Wagner, O. O. Yang, E. A. Zepeda, Y. Ge, S. A. Kalams, B. D. Walker, M. S. Pasternack, and A. D. Luster. Beta-Chemokines Are Released from HIV-1-Specific Cytolytic T Cell Granules Complexed to Proteoglycans. Nature, 391:908-911, 1998. PubMed ID: 9495345. Show all entries for this paper.

Displaying record number 62781

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	assay or method development, protective allele

Notes

NL4-3 Gag polyprotein random mutagenesis, high-throughput fitness profiling and in silico prediction of MHC-peptide binding affinity revealed that mutations in CTL epitopes presented by protective MHC-I alleles, vs. non-protective alleles, showed greater loss of experimental replicative capacity and lower levels of predicted reduction in MHC-I binding affinity. Together, these two variables could predict protectiveness of MHC-I alleles in a linear regression model. Analyses of intraperson viral evolution in 4 LTNP vs. 4 paired progressor subjects further supported paper conclusions.
After mutagenesis and passaging through human T cells, 63 single nucleotide mutations were observed in epitope IEIKDTKEAL (known to bind to B4001) with a log transformation of mean fitness score, relative to NL4-3, of -0.2820.

References

Du2017 Yushen Du, Tian-Hao Zhang, Lei Dai, Xiaojuan Zheng, Aleksandr M. Gorin, John Oishi, Ting-Ting Wu, Janice M. Yoshizawa, Xinmin Li, Otto O. Yang, Otoniel Martinez-Maza, Roger Detels, and Ren Sun. Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T-Lymphocyte Escape of HIV-1 Gag Epitopes. mBio, 8(6), 28 Nov 2017. PubMed ID: 29184023. Show all entries for this paper.

Displaying record number 61285

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HXB2 Location	Gag(92-101) p17(92-101) DNA(1063..1092)	Gag Epitope Map
Author Location	p17(92-101 NL4-3)
Epitope	`IEIKDTKEAL`	Epitope Alignment
Epitope Name	IL10
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	epitope processing

Notes

107 HLA-A*02-restricted epitopes of varying lengths (novel, nested or overlapping) were discovered by using mass spectroscopy to identify peptides bound to HLA on 3 kinds of HIV-infected cells (66 from 293T cells, 20 from a B cell line, B-MDC, and 39 from primary CD4+ T cells). 80-91% of peptides partly overlapped known reported epitopes by >5 aa, while 5-20% were novel. Eluted peptides tended to cluster in nested groups.
Majority of peptides isolated were from Gag and Pol, while Gag peptides from p15 outnumbered those from the more immunogenic p24. 19/23 peptides were tested and were immunogenic. Cytosolic processing and degradation was confirmed.
Highly immunogenic Gag-p17 epitope IEIKDTKEAL was naturally processed and eluted from live 293T cells.

References

Rucevic2016 Marijana Rucevic, Georgio Kourjian, Julie Boucau, Renata Blatnik, Wilfredo Garcia Bertran, Matthew J. Berberich, Bruce D. Walker, Angelika B. Riemer, and Sylvie Le Gall. Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses. J. Virol., 90(19):8605-8620, 1 Oct 2016. PubMed ID: 27440904. Show all entries for this paper.