By Steven Jacobson , Gerald

The HLA D/DR region of the human major histocompatibility complex encodes a family of highly polymorphic, human "Ia-like" molecules that function as genetic restriction elements in a variety of immune phenomena (1, 2). Correlations have been demonstrated between disease susceptibility and particular HLA D/DR antigens (1, 3, 4). Recent evidence (5-7) has demonstrated a considerable heterogeneity within serologically defined clusters of HLA-DR antigens. Individuals who are identical serologically can be shown to be distinct by the mixed lymphocyte reaction (MLR), thus defining unique HLA-D antigens. The view that HLA-DR is supertypic to the MLR-defined HLA-D specificities is supported by biochemical studies using two-dimensional polyacrylamide gels of immunoprecipitated Ia-like molecules from cell lines derived from phenotypically homozygous typing cell donors (homozygous cell lines, HCL). An analysis of the DR/3 chain patterns representative of different HLA-D clusters demonstrated a precise correlation with the HLA-D phenotype of the homozygous typing cell (HTC) donor; i.e., HLA-D specificities reflected structural variations in the DR /3 chains (6, 7). This heterogeneity within a single DR haplotype is central to the concept that Ia structural diversity may account for those polymorphic determinants that are important in Ia-controlled immune phenomena and HLA D/DR disease susceptibility. We have used (8) HLA-DR2, OKT4 + cytotoxic T lymphocytes (CTL) specific for measles virus as the immunologically reactive cell population to investigate which HLA-DR structural epitopes can serve as genetic restriction elements for these HLA class II-restricted CTL clones. The HLA-DR2 serotype includes up to three separate sets of Ia-like molecules that are expressed on HLA-DR2 HTC lines (7). Two distinct/3 chains (DR/31 and DR/32) were present on most HLADR2 cell lines (7). DR/31 did not vary among eight HLA-DR2 HCL tested, while DR/32 was electrophoretically variable among the DR2 cells examined (7). The