I chose to specialize in rheumatology because of the interesting and diverse manifestations of autoimmunity. However, these diseases are poorly characterized in basic immunologic terms- even diseases with a high prevalence in the population, such as rheumatoid arthritis. Thus, I seek a career in academic medicine doing research in the field of autoimmunity/rheumatology. I expect to spend the majority of my time in basic research. My post-doctoral training in the laboratory of Alexander Rudensky, Ph.D., in the Department of Immunology will facilitate my development into an independent principle investigator at an academic institution. My first years in the laboratory were spent exploring the role of lysosomal proteases on antigen processing. My current proposal will investigate the antigen specificity of CD25+ CD4+ T regulatory cells. The CD25+ subset of CD4+ T cells is potent immune suppressors that prevent the development of spontaneous autoimmunity such as arthritis, colitis, and diabetes. CD25+ T cells may develop because of T cell receptor (TCR) recognition of autoantigens, some which may be tissue specific. However, the identity, spectrum, and tissue expression of these autoantigens are completely unknown. The goal of this proposal is to understand the antigen specificity of CD25+ T cells. As CD25+ T cells are anergic in vivo and in vitro, we will develop methods to select for autoreactive TCRs. Individual TCRs can then be characterized for antigen or tissue specificity. This will allow generation of monoclonal CD25+ T cell populations, which will permit analysis of their development, trafficking, activation, and function. Understanding the antigen specificity of this important endogenous T cell suppressor may facilitate the development of disease specific treatments without broad immuno-suppressive side effects.
