%0 Journal Article
%T HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1
%A Marcus Altfeld
%A Elizabeth T Kalife
%A Ying Qi
%A Hendrik Streeck
%A Mathias Lichterfeld
%A Mary N Johnston
%A Nicole Burgett
%A Martha E Swartz
%A Amy Yang
%A Galit Alter
%A Xu G Yu
%A Angela Meier
%A Juergen K Rockstroh
%A Todd M Allen
%A Heiko Jessen
%A Eric S Rosenberg
%A Mary Carrington
%A Bruce D Walker
%J PLOS Medicine
%D 2006
%I Public Library of Science (PLoS)
%R 10.1371/journal.pmed.0030403
%X 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.
%U http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0030403