The Role of Class II Molecules in Development of Insulin-Dependent Diabetes Mellitus in Mice, Rats and Humans
The major histocompatibility complex (MHC) represents a genetic risk factor for most known autoimmune diseases. More and more evidence implicates the class II region of the MHC in susceptibility in diseases such as insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, and pemphigus vulgaris (for review see TODD et al. 1988). The gene products of this region are highly polymorphic and each individual expresses one or two alleles at each locus. Their function is the regulation of the immune response by binding fragments of proteins (peptides) with many different sequences and presenting them to the T cell receptor (TCR) which is expressed by T lymphocytes. Due to the polymorphism of class II molecules, each molecule binds a specific set of peptides (BUUS et al. 1987). These molecules are selective, but relatively nonspecific peptide receptors expressed on B lymphocytes, macrophages, and other cells collectively termed antigen presenting cells (APC’c) (UNANUE and ALLEN 1987). T cells expressing the surface marker CD4 represent the predominant type of T cells which interact with class II expressing cells. After formation of the trimolecular complex between TCR, MHC class II antigen, and peptide, T cell proliferation and differentiation is initiated.
KeywordsArthritis Manifold Recombination Serine Proline
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