CHARACTERIZATION OF TWO SPONTANEOUS IN VIVO VARIANTS CARRYING ALTERED H-2D(B) GENE PRODUCTS (MHC, H-2 MUTANTS, PEPTIDE MAP)

Abstract

The murine major histocompatibility complex (MHC) located on chromosome 17 is a highly polymorphic complex of genes involved in recognition and regulation of the immune system. A number of spontaneous in vivo variants of this complex have arisen, most occurring in the Class I antigens responsible for transplant rejection and associative immune recognition. These variants demonstrate major alterations in the biological functions of the molecules involved. The biochemical analysis of these variants has helped to answer fundamental questions on structure-function relationships in Class I molecules.;In the present study, two variants in the D gene from the C57BL/6 strain are examined. These mutant strains H-2('bm13) and H-2('bm14), show significant alterations in their ability to be recognized by either antibodies or killer T cells directed against the normal D molecule from the parent strain. This thesis describes the alterations of the D molecule from the mutant mouse strains by fluorescent antibody binding studies, lectin binding studies and peptide analyses. Analysis of the altered peptides allowed localization of differences in the mutant molecules. Partial determination of the primary structure of the alterations of both mutants and the attempts to clone the gene coding for the molecule produced by one of the mutant mouse strains are described.