Antigen Processing & Recognition

BIOGRAPHY

Contact information
Smith 514
1 Jimmy Fund Way
Boston MA 02115
Fax 617-525-1010

My laboratory conducts basic research into the molecular and cellular mechanisms of immune recognition of glycolipid antigens. Recent studies of T cell responses to bacterial antigens have uncovered a previously unknown pathway for antigen presentation by a family of proteins known collectively as CD1. CD1 proteins are related to the major histocompatibility complex (MHC) class I and class II encoded antigen presenting molecules. However, unlike MHC class I and II that present peptide antigens, CD1 presents glycolipids for specific T cell recognition. We have identified a new family of the foreign glycolipids presented by CD1b to be glucose monomycolates and determined the specific molecular features of these antigens that activate an immune response (Moody et al. Science 278:283-8). Definition of the antigenic epitopes on these glycolipids clarifies the general molecular mechanism by which CD1 proteins present antigens to T cells. We have recently CD1c to be a family of isoprenoid glycolipids that is conserved throughout eukaryotes, including humans (Moody et al. Nature, 404:884). This expands the realm of targets of the human T cell response to include self glycolipids, suggesting a role of CD1 in autoimmunity and immunoregulation. Current studies are aimed at defining the molecular pathways by which mycobacteria synthesize glycosylated mycolates (Moody et al., J Exp Med 192:965-76), the cellular pathway by which glycolipids are taken up by cells, the molecular basis by which T cells discriminate self from foreign glycolipids (Moody et al. Immunol Rev 172:285-296) and the role of microbial infection in controlling dendritic cell maturation. The long term goal of these studies is to develop a detailed understanding of how the immune system specifically recognizes and responds to glycolipids and how these glycolipids function in the pathogenesis of infectious and autoimmune diseases.