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Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection
BACKGROUND: A dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell resp...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661367/ https://www.ncbi.nlm.nih.gov/pubmed/19352428 http://dx.doi.org/10.1371/journal.pone.0005013 |
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author | Ramduth, Danni Day, Cheryl L. Thobakgale, Christina F. Mkhwanazi, Nompumelelo P. de Pierres, Chantal Reddy, Sharon van der Stok, Mary Mncube, Zenele Nair, Kriebashne Moodley, Eshia S. Kaufmann, Daniel E. Streeck, Hendrik Coovadia, Hoosen M. Kiepiela, Photini Goulder, Philip J. R. Walker, Bruce D. |
author_facet | Ramduth, Danni Day, Cheryl L. Thobakgale, Christina F. Mkhwanazi, Nompumelelo P. de Pierres, Chantal Reddy, Sharon van der Stok, Mary Mncube, Zenele Nair, Kriebashne Moodley, Eshia S. Kaufmann, Daniel E. Streeck, Hendrik Coovadia, Hoosen M. Kiepiela, Photini Goulder, Philip J. R. Walker, Bruce D. |
author_sort | Ramduth, Danni |
collection | PubMed |
description | BACKGROUND: A dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor have clade C HIV-1–specific CD4+ T cell epitopes, likely a vital component of an effective global HIV-1 vaccine, been identified. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular cytokine staining was conducted on 373 subjects with chronic, untreated clade C infection to assess interferon-gamma (IFN-γ) responses by CD4+ T cells to pooled Gag peptides and to determine their association with viral load and CD4 count. Gag-specific IFN-γ–producing CD4+ T cell responses were detected in 261/373 (70%) subjects, with the Gag responders having a significantly lower viral load and higher CD4 count than those with no detectable Gag response (p<0.0001 for both parameters). To identify individual peptides targeted by HIV-1–specific CD4+ T cells, separate ELISPOT screening was conducted on CD8-depleted PBMCs from 32 chronically infected untreated subjects, using pools of overlapping peptides that spanned the entire HIV-1 clade C consensus sequence, and reconfirmed by flow cytometry to be CD4+ mediated. The ELISPOT screening identified 33 CD4+ peptides targeted by 18/32 patients (56%), with 27 of the 33 peptides located in the Gag region. Although the breadth of the CD4+ responses correlated inversely with viral load (p = 0.015), the magnitude of the response was not significantly associated with viral load. CONCLUSIONS/SIGNIFICANCE: These data indicate that in chronic untreated clade C HIV-1 infection, IFN-γ–secreting Gag-specific CD4+ T cell responses are immunodominant, directed at multiple distinct epitopes, and associated with viral control. |
format | Text |
id | pubmed-2661367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26613672009-04-08 Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection Ramduth, Danni Day, Cheryl L. Thobakgale, Christina F. Mkhwanazi, Nompumelelo P. de Pierres, Chantal Reddy, Sharon van der Stok, Mary Mncube, Zenele Nair, Kriebashne Moodley, Eshia S. Kaufmann, Daniel E. Streeck, Hendrik Coovadia, Hoosen M. Kiepiela, Photini Goulder, Philip J. R. Walker, Bruce D. PLoS One Research Article BACKGROUND: A dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor have clade C HIV-1–specific CD4+ T cell epitopes, likely a vital component of an effective global HIV-1 vaccine, been identified. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular cytokine staining was conducted on 373 subjects with chronic, untreated clade C infection to assess interferon-gamma (IFN-γ) responses by CD4+ T cells to pooled Gag peptides and to determine their association with viral load and CD4 count. Gag-specific IFN-γ–producing CD4+ T cell responses were detected in 261/373 (70%) subjects, with the Gag responders having a significantly lower viral load and higher CD4 count than those with no detectable Gag response (p<0.0001 for both parameters). To identify individual peptides targeted by HIV-1–specific CD4+ T cells, separate ELISPOT screening was conducted on CD8-depleted PBMCs from 32 chronically infected untreated subjects, using pools of overlapping peptides that spanned the entire HIV-1 clade C consensus sequence, and reconfirmed by flow cytometry to be CD4+ mediated. The ELISPOT screening identified 33 CD4+ peptides targeted by 18/32 patients (56%), with 27 of the 33 peptides located in the Gag region. Although the breadth of the CD4+ responses correlated inversely with viral load (p = 0.015), the magnitude of the response was not significantly associated with viral load. CONCLUSIONS/SIGNIFICANCE: These data indicate that in chronic untreated clade C HIV-1 infection, IFN-γ–secreting Gag-specific CD4+ T cell responses are immunodominant, directed at multiple distinct epitopes, and associated with viral control. Public Library of Science 2009-04-07 /pmc/articles/PMC2661367/ /pubmed/19352428 http://dx.doi.org/10.1371/journal.pone.0005013 Text en Ramduth et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ramduth, Danni Day, Cheryl L. Thobakgale, Christina F. Mkhwanazi, Nompumelelo P. de Pierres, Chantal Reddy, Sharon van der Stok, Mary Mncube, Zenele Nair, Kriebashne Moodley, Eshia S. Kaufmann, Daniel E. Streeck, Hendrik Coovadia, Hoosen M. Kiepiela, Photini Goulder, Philip J. R. Walker, Bruce D. Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection |
title | Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection |
title_full | Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection |
title_fullStr | Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection |
title_full_unstemmed | Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection |
title_short | Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection |
title_sort | immunodominant hiv-1 cd4+ t cell epitopes in chronic untreated clade c hiv-1 infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661367/ https://www.ncbi.nlm.nih.gov/pubmed/19352428 http://dx.doi.org/10.1371/journal.pone.0005013 |
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