A nonprogressive clinical course in HIV-infected individuals expressing human leukocyte antigen B57/5801 is associated with preserved CD8+ T lymphocyte responsiveness to the HW9 epitope in Nef

J Infect Dis. 2008 Mar 15;197(6):871-9. doi: 10.1086/528695.


The human leukocyte antigen (HLA) B57 allele and the closely related HLA-B5801 allele are overrepresented among human immunodeficiency virus type 1 (HIV-1)-infected individuals with a long-term nonprogressive clinical course of disease (known as "long-term nonprogressors" [LTNPs]). These alleles are, however, also present among individuals with normal disease progression (known as "progressors"). In a comparison of HLA-B57/5801-expressing progressors and LTNPs, we observed a similar prevalence of escape mutations in 4 Nef epitopes and a similar reactivity of CD8+ T cells against 3 of 4 of these epitopes and their autologous escape variants. However, LTNPs tended to have frequent and preserved CD8+ T cell interferon-gamma responses against the wild-type HW9 Nef epitope, whereas progressors did not maintain a specific CD8+ T cell response. This finding is in line with the findings of a more exhausted phenotype of CD8+ T cells in progressors, as is demonstrated by their enhanced level of expression of inhibitory receptor "programmed death 1" (PD-1). The results of the present study suggest that preservation of HW9-specific T cell responses is associated with a more benign clinical course of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology
  • Apoptosis Regulatory Proteins / biosynthesis
  • Apoptosis Regulatory Proteins / immunology
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV Long-Term Survivors
  • HIV-1 / immunology*
  • HLA-B Antigens / biosynthesis*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology
  • Humans
  • Programmed Cell Death 1 Receptor
  • T-Lymphocytes, Cytotoxic / immunology*
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / immunology*


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • Epitopes, T-Lymphocyte
  • HLA-B Antigens
  • HLA-B57 antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1