Genetic and molecular analyses of lymphocyte-defined HLA-D region specificities

Determinants encoded in the HLA-D region have been studied with both cellular (PLT) and molecular (SDS-IEF) methods. When the PLT response against a lymphoblastoid cell line was analyzed by limiting dilution culture and determination of the reactivity of individual cultures against a panel of loss mutants of the initial stimulating LCL, a large fraction of the cultures showed the same pattern, apparently recognizing a determinant associated with DR. In two-dimensional gel analysis of several DR4-positive HLA-D region homozygous cells, the IEF pattern of the DR beta chain correlated with the Dw specificity expressed by the cell. These two pieces of evidence suggest that, although many determinants may contribute to reactivity in mixed leucocyte culture or PLT, an immunodominant determinant associated with the DR beta chain may be the most important single factor in the assignment of Dw specificity.