1987 Philip Levine award lecture. MHC haplotypes in biology and medicine.

(1) The MHC genes or genes within or near the MHC region are involved in the immune response. The polymorphism of the MHC loci can be used as markers for immune response because the recognition of antigens involves their interaction with the MHC antigens. Specific portions of an antigen bind to the polymorphic region of class II molecules. Identification of an MHC class II molecule with a peptide results in a lack of an immune response as a result of self-tolerance. Similarities, but not identity of these molecules, result in immune responses restricted by the variable region of the MHC (class II molecule). This also explains a high repertoire of alloreactive T-cells. (2) By virtue of their restriction of the immune response to foreign antigens that cross-react with self-antigen, the MHC genes or genes within or near the MHC region show an association with the autoimmune diseases. (3) Several alleles encoded by different MHC loci are found nonrandomly associated at the population level. The resulting haplotypes could predict identity of segments of chromosome 6 among unrelated persons. (4) Matching of nonrandomly associated alleles (extended haplotypes) can serve potentially for selection of donors for allotransplantation, especially of bone marrow. (5) Several diseases associated with alleles of the class II MHc loci, and at least in the case of the lack of response to hepatitis B vaccine, have been shown to be more significantly associated with extended haplotypes. In such cases, the extended haplotypes may contain a susceptibility MHC allele of a known MHC locus or may contain a susceptibility gene of a yet undiscovered locus.