Mediation by HLA-DM of dissociation of peptides from HLA-DR

Nature. 1995 Jun 29;375(6534):802-6. doi: 10.1038/375802a0.

Abstract

Human leukocyte antigen (HLA)-DM is an unconventional major histocompatibility complex (MHC) class II heterodimer that is important for B-cell-mediated antigen processing and presentation to MHC class II-restricted T cells. HLA-DM is encoded by two genes, DMA and DMB, which map to the MHC class II region, and shares some homology with MHC class I and class II proteins. Here we define the biochemical role of HLA-DM. Recombinant soluble HLA-DM heterodimers have been purified from culture supernatants of insect cell transformants. At pH 5.0, they induce the dissociation of a subset of peptides bound to HLA-DR, including a nested set of class-II-associated invariant chain peptides (CLIP). This process liberates HLA-DR and leads to the enhanced binding of exogenous peptides.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation, B-Lymphocyte*
  • B-Lymphocytes / immunology*
  • Cell Line
  • Drosophila
  • HLA-D Antigens / physiology*
  • HLA-DR Antigens / chemistry
  • HLA-DR Antigens / metabolism*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Molecular Sequence Data
  • Oligopeptides / metabolism*
  • Protein Conformation
  • Transformation, Genetic

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • H2-M antigens
  • HLA-D Antigens
  • HLA-DM antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Oligopeptides
  • invariant chain