"Dr. Winchester has had a sustained interest in autoimmunity and autoimmune diseases. His laboratory is focused on understanding the genetic basis of susceptibility to autoimmune disease and the mechanisms responsible for triggering and mediating autoimmune injury. His earlier studies defined the molecular importance of IgG rheumatoid factors in rheumatoid arthritis and other autoantibodies in various human autoimmune diseases. He also introduced the use of F(ab')2fragments into cell surface immunofluorescence. Moreover, Dr. Winchester was one of the first to identify human MHC class II molecules on B cells and monocytes and the first to show that they were expressed on human T cells as markers of activation. As importantly, his studies of the polymorphisms of MHC molecules have provided the basis of establishing the link between MHC genotype and susceptibility to multiple forms of autoimmunity. For example in the late 1980's Dr. Winchester and colleagues showed that susceptibility to rheumatoid arthritis was determined by sequences in the HLA-DR beta chain of MHC class II molecules, and formulated the shared MHC 'epitope' hypothesis. This hypothesis provides a molecular basis for susceptibility to rheumatoid arthritis, implicating a region on the MHC molecule that both binds a peptide side chain and interacts with the TCR. This key discovery has emphasized the importance of the modern means of HLA typing, which involves DNA sequencing of the MHC genes and the theoretical basis for the discovery of antigens that initiate autoimmune disease. More recently, Dr. Winchester has coupled the DNA sequencing of the MHC genes with the analysis and high throughput DNA sequencing of human T cell receptor genes to permit molecular analysis of the cognitive T cell/peptide/MHC recognition events that underlie the role of the adaptive immune system in autoimmunity. "

Pediatrics