HLA-DM induces CLIP dissociation from MHC class II alpha beta dimers and facilitates peptide loading

Cell. 1995 Jul 14;82(1):155-65. doi: 10.1016/0092-8674(95)90061-6.


Human leukocyte antigen DM (HLA-DM) molecules are structurally related to classical MHC class II molecules and reside in the lysosome-like compartment where class II-restricted antigen processing is thought to occur. Mutant cell lines lacking HLA-DM are defective in antigen processing and accumulate class II molecules associated with a nested set of invariant chain-derived peptides (class II-associated invariant chain peptides, CLIP). Here we show that HLA-DM catalyzes the dissociation of CLIP from MHC class II-CLIP complexes in vitro and facilitates the binding of antigenic peptides. The reaction has an acidic pH optimum, consistent with its occurrence in a lysosome-like compartment in vivo. Antibody blocking experiments suggest that a transient interaction between HLA-DM and the MHC class II-CLIP complex is required.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation, B-Lymphocyte*
  • Bacterial Outer Membrane Proteins / metabolism
  • Chlamydia trachomatis
  • HLA-D Antigens / metabolism*
  • HLA-DR3 Antigen / metabolism
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Hybrid Cells
  • Hydrogen-Ion Concentration
  • Mice
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / metabolism*
  • Porins*
  • T-Lymphocytes


  • Antigens, Differentiation, B-Lymphocyte
  • Bacterial Outer Membrane Proteins
  • H2-M antigens
  • HLA-D Antigens
  • HLA-DM antigens
  • HLA-DR3 Antigen
  • Histocompatibility Antigens Class II
  • Peptides
  • Porins
  • invariant chain
  • omp1 protein, Chlamydia trachomatis