Soluble beta 2-microglobulin-free class I heavy chains are released from the surface of activated and leukemia cells by a metalloprotease

J Biol Chem. 1994 Mar 4;269(9):6689-94.

Abstract

Regulation of the expression of major histocompatibility complex (MHC) class I heavy chains not associated with beta 2-microglobulin (beta 2m) on freshly isolated and in vitro cultured human B and T leukemia cells was analyzed. These beta 2m-free class I heavy chains originate from surface beta 2m-associated MHC class I molecules and are expressed as integral membrane glycoproteins on activated, but not resting, cells. We found that the levels of beta 2m-free class I heavy chains can be regulated by proteolytic cleavage and release into the medium of soluble molecules containing the extracellular domains. The release is mediated by a Zn(2+)-dependent, membrane-bound metalloprotease that does not cleave HLA-DR, CD4, and CD71 surface receptors and can be activated by phorbol myristate acetate. Specific cleavage by the metalloprotease occurs at a site close to the papain cleavage site in the alpha 3 domain of class I heavy chains. This site is not accessible to the metalloprotease in beta 2m-associated MHC class I molecules. The dissociation of beta 2m-associated MHC class I molecules and subsequent cleavage of beta 2m-free class I heavy chains may be partially responsible for controlling the levels of MHC class I molecules on the surface of activated cells.

Publication types

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

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • CD4 Antigens / metabolism
  • Flow Cytometry
  • HLA-DR Antigens / metabolism
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / isolation & purification
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Leukemia, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, T-Cell / immunology*
  • Macromolecular Substances
  • Metalloendopeptidases / metabolism*
  • Phenanthrolines / pharmacology
  • Receptors, Transferrin
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured
  • Zinc / pharmacology
  • beta 2-Microglobulin / isolation & purification*

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD4 Antigens
  • CD71 antigen
  • HLA-DR Antigens
  • Histocompatibility Antigens Class I
  • Macromolecular Substances
  • Phenanthrolines
  • Receptors, Transferrin
  • beta 2-Microglobulin
  • Metalloendopeptidases
  • Zinc
  • Tetradecanoylphorbol Acetate