Mhc Class II Genes of Nonhuman Primates

Abstract

In humans the HLA-D region was originally discovered by use of the mixed lymphocyte culture (MLC) test. This assay is based on coculturing lymphocyte suspensions of two unrelated individuals and actually measures the proliferative capacity of T lymphocytes. Normally one uses a so-called one way stimulation, meaning that one of the two cell populations has been inactivated, for instance, by irradiation. As a result the treated cells are unable to proliferate but still have the capacity to stimulate T cells of the second individual. Lymphocytes from HLA-identical siblings generally do not stimulate each other in the MLC whereas lymphocytes from HLA nonidentical individuals do. Since serologically typed HLA-A, -B and -C identical individuals could stimulate each others’ cells, the incompatibility measured in the MLC was assigned to the HLA-D locus on chromosome 6. MHC antigens are inherited in a codominant fashion and as a consequence a given individual may be heterozygous for its HLA-D region products. Lymphocytes derived from donors descending from consanguineous offspring may be truly homozygous for the HLA region. Such homozygous typing cells (HTCs) were initially used to investigate and to inventory the polymorphism of HLA-D locus products. By now, more than 20 different HLA-D specificities have been identified in the human population. In parallel, MLC stimulating determinants have been documented for the chimpanzee and rhesus macaque (Jonker and Balner 1980). An apparently new set of antigens was defined using sera from multiparous women from which all HLA-A, -B and -C reactivity had been depleted. These allo-antisera reactions were found to have good concordance with HLA-D alleles but, moreover, were able to inhibit MLC reactivity. The serologically defined B lymphocyte cell surface antigens detected in this way were designated HLA-DR, standing for HLA-D related.