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.