Our HLA laboratory in collaboration with the Center for Blood Research provides s large number of genotyped families for all of the known genetic markers of human chromosome 6, including HLA, GLO, and the complotypes (a combination of typing for four different loci encoding for complement proteins C2, Bf, C4A, and C4B). We have developed a large group of serological reagents (antibodies to HLA antigens, alloantibodies, and monoclonal antibodies) to study the complexity of the histocompatibility antigens, in particular, the genetic complexity of the HLA-D/DR region. These reagents will be useful in understanding not only the genetics of the HLA region, but also the biological role of the HLA molecules. In this regard, we have developed a large number of T-cell clones specific for antigen (tetanus toxoid), which proliferate after antigen presentation by macrophages. The antibodies are useful tools in studying the role of HLA-DR in cell-to-cell interaction. We have studied, in a different group of experiments, the phenomenon of linkage disequilibrium or nonrandom association of alleles by examining a large number of families. These studies have permitted us to describe eight extended haplotypes which have been useful in the definition of such diseases as diabetes mellitus (insulin-dependent) and congenital adrenal hyperplasia. One of the haplotypes associated with diabetes (B8, DR3, SCO1, GLO2) is the first human example of a t-murine mutant. These findings will be useful in trying to understand the evolution of humans or the population admixtures (founder effects). We have also used immunoprecipitation by monoclonal antibodies to Class I histocompatibility antigens and isoelectrofocusing to discover variants of known Class I alloantigens encoded by the HLA-B locus. Of interest is the fact that such variants distinguish Caucasians from Orientals. (LB)
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