The antigenic structure of HLA-A2: an analysis with competitive binding assays and monoclonal antibodies

Twelve mouse monoclonal antibodies against HLA-A2 were analyzed by competitive binding assays on cells. The A2 molecule was found to have two topologically distinct regions of highly specific alloantigenic determinants. One region encompasses determinants shared with HLA-A28 and the other contains determinants shared with HLA-B17 and a variant, A28*, of HLA-A28. Each of these two alloantigenic regions is more closely associated with a different broadly polymorphic determinant shared by many HLA gene products. The topographic relationship between the two alloantigenic regions, four monomorphic determinants, and the carbohydrate moiety of the HLA heavy chain was also assessed. All the antigenic determinants preferentially associate with one or other of the two alloantigenic regions. An analysis of these results with reference to the amino acid sequences of A2 and A28 suggests a working hypothesis whereby the A2,A28*,B17 region primarily involves residues of the NH2-terminal or first domain, and that the A2,A28 region primarily involves residues of the second domain of the A2 heavy chain.