Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection
Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection...
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The Rockefeller University Press
2001
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193346/ |
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pubmed-21933462008-04-14 Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection Goulder, Philip J.R. Altfeld, Marcus A. Rosenberg, Eric S. Nguyen, Thi Tang, Yanhua Eldridge, Robert L. Addo, Marylyn M. He, Suqin Muckerjee, Joia S. Phillips, Mary N. Bunce, Michael Kalams, Spyros A. Sekaly, Rafick P. Walker, Bruce D. Brander, Christian Original Article Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection. In this study, HIV-1 infection in persons expressing human histocompatibility leukocyte antigen (HLA)-A*0201 was used as a means of addressing this issue. In chronic infection, the dominant HLA-A*0201–restricted CTL response is directed towards the epitope SLYNTVATL (“SL9”) in p17 Gag (residues 77–85). This epitope is targeted by 75% of HLA-A*0201–positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive infection. Despite using the highly sensitive peptide–major histocompatibility complex tetramer and intracellular cytokine assays, responses to the SL9 epitope were not detectable in any of 11 HLA-A*0201–positive subjects with acute HIV-1 infection (P = 2 × 10−6), even when assays were repeated using the SL9 peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other epitopes were evident in 7 of the 11 A*0201–positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in chronic infection may differ substantially from those that constitute the initial antiviral CTL response. This finding is an important consideration in vaccine design and in the evaluation of vaccine candidates. The Rockefeller University Press 2001-01-15 /pmc/articles/PMC2193346/ /pubmed/11148222 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Goulder, Philip J.R. Altfeld, Marcus A. Rosenberg, Eric S. Nguyen, Thi Tang, Yanhua Eldridge, Robert L. Addo, Marylyn M. He, Suqin Muckerjee, Joia S. Phillips, Mary N. Bunce, Michael Kalams, Spyros A. Sekaly, Rafick P. Walker, Bruce D. Brander, Christian |
| spellingShingle |
Goulder, Philip J.R. Altfeld, Marcus A. Rosenberg, Eric S. Nguyen, Thi Tang, Yanhua Eldridge, Robert L. Addo, Marylyn M. He, Suqin Muckerjee, Joia S. Phillips, Mary N. Bunce, Michael Kalams, Spyros A. Sekaly, Rafick P. Walker, Bruce D. Brander, Christian Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection |
| author_facet |
Goulder, Philip J.R. Altfeld, Marcus A. Rosenberg, Eric S. Nguyen, Thi Tang, Yanhua Eldridge, Robert L. Addo, Marylyn M. He, Suqin Muckerjee, Joia S. Phillips, Mary N. Bunce, Michael Kalams, Spyros A. Sekaly, Rafick P. Walker, Bruce D. Brander, Christian |
| author_sort |
Goulder, Philip J.R. |
| title |
Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection |
| title_short |
Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection |
| title_full |
Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection |
| title_fullStr |
Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection |
| title_full_unstemmed |
Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection |
| title_sort |
substantial differences in specificity of hiv-specific cytotoxic t cells in acute and chronic hiv infection |
| description |
Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection. In this study, HIV-1 infection in persons expressing human histocompatibility leukocyte antigen (HLA)-A*0201 was used as a means of addressing this issue. In chronic infection, the dominant HLA-A*0201–restricted CTL response is directed towards the epitope SLYNTVATL (“SL9”) in p17 Gag (residues 77–85). This epitope is targeted by 75% of HLA-A*0201–positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive infection. Despite using the highly sensitive peptide–major histocompatibility complex tetramer and intracellular cytokine assays, responses to the SL9 epitope were not detectable in any of 11 HLA-A*0201–positive subjects with acute HIV-1 infection (P = 2 × 10−6), even when assays were repeated using the SL9 peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other epitopes were evident in 7 of the 11 A*0201–positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in chronic infection may differ substantially from those that constitute the initial antiviral CTL response. This finding is an important consideration in vaccine design and in the evaluation of vaccine candidates. |
| publisher |
The Rockefeller University Press |
| publishDate |
2001 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193346/ |
| _version_ |
1611431037735272448 |