Dr. Winchester has had a sustained interest in human autoimmunity. His earlier studies defined the molecular importance of rheumatoid factors, other autoantibodies and immune complexes in human disease. Moreover, Dr. Winchester was involved in the early identification and tissue expression of human MHC class II molecules. As importantly, his studies of the polymorphisms of MHC molecules have provided the basis of establishing the link between MHC genotype and susceptibility to autoimmunity. For example in the late 1980's Dr. Winchester and colleagues showed that susceptibility to rheumatoid arthritis was determined by sequences in the b chain of MHC class II molecules.

This observation led to the shared MHC 'epitope' hypothesis which provides a molecular basis for susceptibility to rheumatoid arthritis associated with a region on the MHC molecule involved in both binding of the peptide and interacting with the TCR. This seminal 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. In recent years Dr. Winchester has also focused on DNA and peptide sequence analysis of T cell receptor a and b chains in order to define the changes in the TCR repertoire associated with autoimmunity.

Email: rjw8@cumc.columbia.edu