HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1.

HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1.

<h4>Background</h4>Very little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression.<h4>Methods and findings</h4>In a cohort of 104 in...

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Main Authors: 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, Bruce D Walker
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2006-10-01
Series:PLoS Medicine
Online Access:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.0030403&type=printable
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Summary:<h4>Background</h4>Very little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression.<h4>Methods and findings</h4>In a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8(+) T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized. Certain HLA alleles consistently contributed more than others to the total virus-specific CD8(+) T cell response during primary infection, and also reduced the absolute magnitude of responses restricted by other alleles if coexpressed in the same individual, consistent with immunodomination. Furthermore, individual HLA class I alleles that have been associated with slower HIV-1 disease progression contributed strongly to the total HIV-1-specific CD8(+) T cell response during primary infection.<h4>Conclusions</h4>These data demonstrate consistent immunodominance patterns of HIV-1-specific CD8(+) T cell responses during primary infection and provide a mechanistic explanation for the protective effect of specific HLA class I alleles on HIV-1 disease progression.
ISSN:1549-1277
1549-1676

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