HLA-DM induces CLIP dissociation from MHC class II alpha beta dimers and facilitates peptide loading.
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.
Denzin
L K
LK
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510-8011, USA.
Cresswell
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002692:Chlamydia trachomatis; D006681:HLA-D Antigens / Q000378:metabolism*; D015803:HLA-DR3 Antigen / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D006822:Hybrid Cells; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D018272:Porins; D013601:T-Lymphocytes
D000944:Antigens, Differentiation, B-Lymphocyte; D001425:Bacterial Outer Membrane Proteins; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D015803:HLA-DR3 Antigen; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D018272:Porins; C045084:invariant chain; C071677:omp1 protein, Chlamydia trachomatis