HLA-specific intracellular epitope processing shapes an immunodominance pattern for HLA-B*57 that is distinct from HLA-B*58:01

J Virol. 2013 Oct;87(19):10889-94. doi: 10.1128/JVI.01122-13. Epub 2013 Jul 17.

Abstract

HLA-B*57 is strongly associated with immune control of HIV and delayed AIDS progression. The closely related, but less protective, HLA-B*58:01 presents similar epitopes, but HLA-B*58:01(+) individuals do not generate CD8(+) T cells targeting the KF11-Gag epitope, which has been linked to low viremia. Here we show that HLA-B*58:01 binds and presents KF11 peptide, but HIV-infected HLA-B*58:01(+) cells fail to process KF11. This unexpected finding demonstrates that immunodominance patterns can be influenced by intracellular events independent of HLA binding motifs.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Epitopes / immunology*
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HLA-B Antigens / immunology*
  • HLA-B Antigens / metabolism
  • Humans
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Viral Load
  • Viremia / immunology*
  • Viremia / metabolism
  • gag Gene Products, Human Immunodeficiency Virus / immunology
  • gag Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Epitopes
  • HLA-B Antigens
  • HLA-B*58:01 antigen
  • HLA-B57 antigen
  • Peptide Fragments
  • gag Gene Products, Human Immunodeficiency Virus