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

PLoS Med. 2006 Oct;3(10):e403. doi: 10.1371/journal.pmed.0030403.


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 types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / genetics*
  • Acquired Immunodeficiency Syndrome / immunology*
  • Alleles
  • Antigenic Variation
  • CD8-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Disease Progression
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Genes, MHC Class I / immunology
  • HIV Infections / immunology
  • HIV-1 / immunology*
  • HLA Antigens / genetics*
  • Humans
  • Immunodominant Epitopes / immunology
  • Male
  • Proportional Hazards Models


  • Epitopes, T-Lymphocyte
  • HLA Antigens
  • Immunodominant Epitopes