Association between HLA-DM and HLA-DR in vivo.
The exchange of HLA class II-associated invariant chain peptides (CLIP) for cognate peptide is catalyzed by HLA-DM under acidic conditions in vitro by an unknown mechanism. Here, we show an association between HLA-DM and HLA-DR in vivo by coprecipitation of the two heterodimers. The association is favored at low pH and in the nonionic detergent digitonin. Most DM-DR complexes are isolated from dense subcellular fractions. Recovery of HLA-DM by the conformation-dependent DR3 monoclonal antibody 16.23 suggests an association with HLA-DR heterodimers beyond the stage at which CLIP is released. The additional N-linked glycan on mutant DR3 molecules isolated from the 10.24.6 cell line, which interferes with DM-enhanced CLIP release from DR3 in vitro, also affects the DM-DR interaction.
Sanderson
F
F
Human Immunogenetics Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Thomas
C
C
Neefjes
J
J
Trowsdale
J
J
D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011940:Receptor Aggregation; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D006681:HLA-D Antigens