Control of HIV-1 by an HLA-B*52:01-C*12:02 Protective Haplotype

J Infect Dis. 2017 Dec 12;216(11):1415-1424. doi: 10.1093/infdis/jix483.

Abstract

HLA-B*52:01-C*12:02, which is found in approximately 20% of all Japanese persons, is well known to be associated with ulcerative colitis and Takayasu arteritis. This haplotype is also known to be protective in individuals infected with human immunodeficiency virus (HIV) type 1. Recent studies showed that HLA-B*52:01-restricted HIV-1-specific T cells suppress HIV-1 and that HLA-C*12:02 together with KIR2DL2 play an important role in natural killer cell-mediated control of HIV-1. However, the role of HLA-C*12:02-restricted cytotoxic T lymphocytes (CTLs) in suppressing HIV-1 replication remains unknown. In the present study, we demonstrated that HLA-C*12:02-restricted CTLs specific for 2 immunodominant epitopes, Pol IY11 and Nef MY9, contributed to the suppression of HIV-1 replication in HIV-1-infected individuals. Further analysis demonstrated that these 2 HLA-C*12:02-restricted CTLs together with 4 HLA-B*52:01-restricted ones effectively suppressed HIV-1 in individuals with the HLA-B*52:01-C*12:02 haplotype. Thus, both HLA-C*12:02 and HLA-B*52:01 alleles contribute to HIV-1 suppression via both HIV-1-specific CTLs and natural killer cells in individuals with this haplotype.

Keywords: CTL; HIV-1; HLA-B*52:01; HLA-C*12:02; haplotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cell Line
  • Chromium / analysis
  • Cytokines / analysis
  • Epitopes, T-Lymphocyte
  • HIV Infections / diet therapy
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HLA-B Antigens / immunology
  • HLA-B Antigens / pharmacology*
  • HLA-B52 Antigen / immunology
  • HLA-B52 Antigen / pharmacology*
  • HLA-C Antigens / immunology
  • HLA-C Antigens / isolation & purification
  • HLA-C Antigens / pharmacology*
  • Haplotypes / immunology*
  • Host-Pathogen Interactions
  • Humans
  • Immunodominant Epitopes / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Receptors, KIR2DL2 / physiology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • Virus Replication / drug effects
  • nef Gene Products, Human Immunodeficiency Virus / immunology
  • nef Gene Products, Human Immunodeficiency Virus / pharmacology
  • pol Gene Products, Human Immunodeficiency Virus / immunology
  • pol Gene Products, Human Immunodeficiency Virus / pharmacology

Substances

  • Cytokines
  • Epitopes, T-Lymphocyte
  • HLA-B Antigens
  • HLA-B*52:01 antigen
  • HLA-B52 Antigen
  • HLA-C Antigens
  • HLA-C*12 antigen
  • Immunodominant Epitopes
  • KIR2DL2 protein, human
  • Receptors, KIR2DL2
  • nef Gene Products, Human Immunodeficiency Virus
  • pol Gene Products, Human Immunodeficiency Virus
  • Chromium