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

Authors

• Marcus Altfeld, Harvard Medical SchoolFollow
• Elizabeth t. Kalife, Harvard Medical School
• Ying Qi, SAIC-Frederick
• Hendrik Streeck, Gemeinschaftspraxis Jessen
• Mathais Lichterfeld, Harvard Medical School
• Mary N. Johnston, Harvard Medical School
• Nicole Burgett, Harvard Medical School
• Martha E. Swartz, Harvard Medical School
• Amy Yang, Harvard Medical School
• Galit Alter, Harvard Medical School
• Xu G. Yu, Harvard Medical School
• Angela Meier, Harvard Medical School
• Juergen K. Rockstroh, University of Bonn
• Todd M. Allen, Harvard Medical School
• Heiko Jessen, Gemeinschaftspraxis Jessen
• Eric S. Rosenberg, Harvard Medical School
• Mary Carrington, National Institutes of HealthFollow
• Bruce D. Walker, Howard Hughes Medical InstituteFollow

Date of this Version

2006

Comments

Published in PLOS Medicine (2006) 3:10, 1851-1864; DOI: 10.1371/journal.pmed.0030403

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.