HLA and Disease: Molecular Basis

The central role played by human leukocyte antigens (HLA) in the antigen-specific immune response is well established. Less well established, especially at the molecular level, is the role played by HLA proteins in the wide range of diseases that have been reported to be either positively or negatively associated with the expression of Particular HLA alleles. Major developments in the field of immunology, some, in fact, stimulated by early observations that certain serologically defined HLA alleles were increased in frequency among individuals affected by a particular disease, have now set the scene for rapid progress in defining at the molecular level the roles played by HLA molecules in disease processes. Extensive mapping of the MHC region has identified multiple loci encoding class I and class II HLA proteins, as well as hundreds of genes that encode non-HLA proteins (see chapter 2). Recent developments in tissue typing techniques have enabled HLA typing to move from serological techniques, based on antibody recognition of conformational epitopes on HLA proteins, to DNA-based techniques that depend on allelic sequence differences. As more highly specific antisera have been found and molecular tissue typing techniques have been increasingly used, the initial groupings of class I and class II HLA proteins have been “split” into multiple closely-related alleles, and additional class I and class II alleles have been identified.