Human major histocompatibility molecules have the intrinsic ability to form homotypic associations.
We have investigated the homotypic associations of major histocompatibilty, class II and class I molecules using immunoprecipitation from detergent solubilised cell extracts. A 120-kDa structure corresponding to an HLA-DR dimer of dimers was immunoprecipitated by the HLA-DR specific mAb L243 from both biotinylated cell-surface and metabolically labeled B cells and transfectant fibroblasts. The thermostability of this structure in SDS was examined. It was detected at 4 degrees C, 22 degrees C, and 37 degrees C, but not at 50 degrees C or 100 degrees C. Experiments performed with L243 Fab fragments and with purified HLA-DR molecules, indicated the presence of HLA-DR dimers of dimers and single heterodimers on B cells. HLA-DQ was also found to form SDS-stable dimers of dimers and single heterodimers on the cell surface of B cells, demonstrating that HLA class II isotypes, other than HLA-DR, also form homotypic associations. Similar experiments performed with HLA class I specific mAb, W632, revealed the existence of a 90 kDa and a 135-kDa structure corresponding to a MHC class I multimers. Under the same conditions, non-MHC molecules such as CD14 were found not to self-associate. These findings indicate that major histocompatibility molecules have the intrinsic ability to form homotypic associations at the cell surface of antigen presenting cells.
Triantafilou
K
K
Department of Biological Sciences, University of Essex, Colchester, United Kingdom. ktrian@essex.ac.uk
Triantafilou
M
M
Wilson
K M
KM
Fernandez
N
N
D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology* / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000276:immunology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C045084:invariant chain