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 so lubilised cell extracts. A 120-kDa structure corresponding to an HLA-DR dim er of dimers was immunoprecipitated by the HLA-DR specific mAb L243 from bo th biotinylated cell-surface and metabolically labeled B cells and transfec tant 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 L it 50 degrees C or 100 degrees C. Experiments performed with L243 Fab fragm ents and with purified HLA-DR molecules, indicated the presence of HLA-DR d imers of dimers and single heterodimers on B cells. HLA-DQ was also found t o form SDS-stable dimers of dimers and single heterodimers on the cell surf ace 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-kD a structure corresponding to a MHC class I multimers. Under the same condit ions, non-MHC molecules such as CD14 were found not to self-associate. Thes e findings indicate that major histocompatibility molecules have the intrin sic ability to form homotypic associations ar the cell surface of antigen p resenting cells. (C) American Society For Histocompatibility and Immunogene tics, 2000. Published by Elsevier Science Inc.