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- Title
HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8<sup>+</sup> T Cell Response against HIV-1.
- Authors
Altfeld, Marcus; Kalife, Elizabeth T.; Ying Qi; Streeck, Hendrik; Lichterfeld, Mathias; Johnston, Mary N.; Burgett, Nicole; Swartz, Martha E.; Amy Yang; Alter, Galit; Yu, Xu G.; Meier, Angela; Rockstroh, Juergen K.; Allen, Todd M.; Jessen, Heiko; Rosenberg, Eric S.; Carrington, Mary; Walker, Bruce D.
- Abstract
Background 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. Methods and Findings 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. Conclusions 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.
- Publication
PLoS Medicine, 2006, Vol 3, Issue 10, p1851
- ISSN
1549-1277
- Publication type
Academic Journal
- DOI
10.1371/journal.pmed.0030403