Presentation to T cells.
laboratory showed that the cellular immune system is capable of not
only recognizing peptides in the context of MHC molecules, but it is
also capable of recognizing lipid antigens in the context of CD1 molecules.
CD1 molecules are MHC class I-like molecules that contain hydrophobic
antigen pockets that bind the lipid tails of antigens, rather than
the side chains and backbone of peptides. The genes encoding the CD1a,
b, c and d molecules represent a distinct lineage of antigen presenting
elements that open T cell recognition to the universe of lipid containing
self and foreign antigens. These lipid antigens include glycolipids,
including sphingolipids, diacylglycerol, lipopeptides and fatty acids
that are found in the cell walls of bacteria and parasites or are self-lipids
in mammalian cells.
laboratory is defining the role of CD1 restricted T cells in adaptive
immunity and innate immunity. We are studying the biochemical and molecular
aspects of antigen delivery, loading and T cell activation in human
in vitro systems and in mouse models. We have defined the intracellular
trafficking of CD1 molecules and demonstrated how they survey endosomal
compartments to intersect and bind antigens and how this process occurs
in infected APCs. Our studies are unfolding how CD1a, b, c mediate
clonally restricted adaptive T cell immunity to microbial lipid antigens
and how NKT cells mediate innate immunity that provides immediate defense
and shapes the subsequent adaptive immune responses.
of Rheumatoid Arthritis.
are studying the immunological basis of inflammatory arthritis. We
found that cadherins, important adhesion molecules in tissue morphogenesis
during development and in the maintenance of tissue architecture in
adults, play a key role in the proliferative and invasive nature of
synoviocytes in rheumatoid arthritis. In the absence of synovial cadherin,
synovial lining formation is attenuated and the inflammatory response
in the joint is abated. These studies now provide an underlying concept
for rheumatoid arthritis in which the pathologic response is dependent
on the reaction of synoviocytes induced by inflammation that can result
in tissue damage. We are now determining how cadherins regulate cell
invasion and inflammation.
B. Brenner, M.D.