Mutagenesis and expression of putative class II susceptibility genes: a "reverse immunogenetics" approach to analysis of HLA and disease

Immune activation events regulated by the human MHC are triggered by interactions between HLA class II molecules, antigenic peptides, and reactive T cells. In most autoimmune diseases, little is known about the latter two elements of this trimolecular complex, while the HLA class II contribution is being deciphered in increasingly sophisticated detail. In two cases in particular, type I diabetes and rheumatoid arthritis, susceptibility is tied to structural elements within specific HLA class II genes. Site-directed mutagenesis and gene expression studies provide a means to directly test the contribution of specific residues within individual candidate disease susceptibility genes to peptide and T cell interactions.