Different in vivo effects of HIV-1 immunodominant epitope-specific cytotoxic T lymphocytes on selection of escape mutant viruses

J Virol. 2010 Jun;84(11):5508-19. doi: 10.1128/JVI.02483-09. Epub 2010 Mar 24.

Abstract

HIV-1 escape mutants are well known to be selected by immune pressure via HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies. The ability of the CTLs to suppress HIV-1 replication is assumed to be associated with the selection of escape mutants from the CTLs. Therefore, we first investigated the correlation between the ability of HLA-A*1101-restricted CTLs recognizing immunodominant epitopes in vitro and the selection of escape mutants. The result showed that there was no correlation between the ability of these CTLs to suppress HIV-1 replication in vitro and the appearance of escape mutants. The CTLs that had a strong ability to suppress HIV-1 replication in vitro but failed to select escape mutants expressed a higher level of PD-1 in vivo, whereas those that had a strong ability to suppress HIV-1 replication in vitro and selected escape mutants expressed a low level of PD-1. Ex vivo analysis of these CTLs revealed that the latter CTLs had a significantly stronger ability to recognize the epitope than the former ones. These results suggest that escape mutations are selected by HIV-1-specific CTLs that have a stronger ability to recognize HIV-1 in vivo but not in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HIV-1 / genetics*
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • HLA-A Antigens
  • HLA-A11 Antigen
  • Immune Evasion / genetics*
  • Immunodominant Epitopes
  • Mutation* / immunology
  • Selection, Genetic / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Virus Replication

Substances

  • HLA-A Antigens
  • HLA-A*11:01 antigen
  • HLA-A11 Antigen
  • Immunodominant Epitopes