HLA-B polymorphisms and intracellular assembly modes

Mol Immunol. 2015 Dec;68(2 Pt A):89-93. doi: 10.1016/j.molimm.2015.07.007. Epub 2015 Jul 31.

Abstract

Human leukocyte antigen (HLA) class I molecules are ligands for antigen receptors of cytotoxic T cells (CTL) and inhibitory receptors of natural killer (NK) cells. The high degree of HLA class I polymorphism allows for the selection of distinct and diverse sets of antigenic peptide ligands for presentation to CTL. The extensive polymorphisms of the HLA class I genes also result in large variations in their intracellular folding and assembly characteristics. Recent findings indicate that North American HLA-B variants differ significantly in the stabilities of their peptide-deficient forms and in the requirements for the endoplasmic reticulum (ER)-resident factor tapasin for proper assembly. In HIV-infected individuals, the presence of tapasin-independent HLA-B allotypes links to more rapid progression to death. Further studies are important to better understand how the intrinsic structural characteristics of HLA class I folding intermediates affect immune responses mediated by CTL and NK cells.

Keywords: AIDS; Calreticulin; ERp57; Endoplasmic reticulum; HIV; HLA-B; MHC class I; Peptide loading complex; TAP transporter; Tapasin.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / genetics*
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology*
  • Cytosol / immunology
  • Cytosol / metabolism
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology*
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / immunology
  • Models, Molecular
  • Peptides / immunology
  • Peptides / metabolism
  • Polymorphism, Genetic*
  • Receptors, Natural Killer Cell / genetics
  • Receptors, Natural Killer Cell / immunology
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • HLA-B Antigens
  • Membrane Transport Proteins
  • Peptides
  • Receptors, Natural Killer Cell
  • tapasin