Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP

Immunity. 1996 Aug;5(2):103-14. doi: 10.1016/s1074-7613(00)80487-2.

Abstract

Assembly of MHC class I-beta 2 microglobulin (beta 2m) dimers in the endoplasmic reticulum involves two chaperones. Calnexin has previously been shown to interact with free class I heavy chains. Here, we show that the related chaperone, calreticulin, binds human class I-beta 2m dimers prior to peptide loading. Calreticulin remains associated with at least a subset of class I molecules when they, in turn, bind to TAP. Further evidence suggests that the interaction of class I-beta 2m dimers with TAP occurs via a novel uncharacterized 48 kDa glycoprotein, tapasin, which can bind independently to TAP and class I-beta 2m-calreticulin complexes. Tapasin is absent from the mutant cell line .220, in which class I-TAP association and peptide loading is defective.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / drug effects
  • ATP-Binding Cassette Transporters / metabolism*
  • Calcium-Binding Proteins / physiology*
  • Calreticulin
  • Cell Line
  • Glycoproteins / physiology*
  • HLA-A Antigens / drug effects
  • HLA-A Antigens / metabolism
  • HLA-B Antigens / drug effects
  • HLA-B Antigens / metabolism
  • HLA-C Antigens / drug effects
  • HLA-C Antigens / metabolism
  • Histocompatibility Antigens Class I / drug effects
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Indolizines / pharmacology
  • Molecular Chaperones / physiology*
  • Mutation
  • Peptides / metabolism
  • Ribonucleoproteins / physiology*
  • beta 2-Microglobulin / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Calcium-Binding Proteins
  • Calreticulin
  • Glycoproteins
  • HLA-A Antigens
  • HLA-A29 antigen
  • HLA-B Antigens
  • HLA-B61 antigen
  • HLA-C Antigens
  • HLA-C*02 antigen
  • Histocompatibility Antigens Class I
  • Indolizines
  • Molecular Chaperones
  • Peptides
  • Ribonucleoproteins
  • TAP1 protein, human
  • beta 2-Microglobulin
  • castanospermine