(1) The basic biology of surface molecules expressed on T lymphocytes
(2) The mechanisms used by T cells to activate and control human immune responses
(3) The pathogenesis of immunological disease including autoimmunity and AIDS
1. Karpusas, M., Y. Hsu, J. Wang, J. Thompson, S. Lederman, L. Chess, and D. Thomas. 2 � crystal structure of an extracellular fragment of human CD40 ligand. Structure 15, October, 1995, 3:1031-1039.
2. Yellin, M., J. Brett, D. Baum, A. Matsushima, M. Szabolcs, D. Stern, L. Chess. Functional Interactions of T Cells with Endothelial Cells: the Role of CD40L-CD40-mediated Signals. J. Exp. Med. 182:1857-1864, 1995.
3. Saha, K., R. Ware, M. Yellin, L. Chess, I. Lowy. Herpesvirus saimiri-Transformed Human CD4+ T cells Can Provide Polyclonal B Cell Help via the CD40 Ligand as well as the TNF-a Pathway and through release of Lymphokines. The Journal of Immunology, 1996, Vol. 157, 4:3876-3885.
4. Jiang, H., Kashleva, H., Xu, L., Forman, J., Flaherty, L., Pernis, B., Braunstein, N. and Chess, L. T Cell Vaccination Induces TCR Vb Specific, Qa-1 Restricted Regulatory CD8+ T cells. Proceedings of the National Academy of Sciences, Vol 95, 4533-4537, April 1998.
5. Bank, I., Bushkin, Y., Kritchevsky, A., Langevitz, P., Book, M., Shenkman, B., Ware, R., and Chess, L. A Novel 26 Kilodalton Antigen Expressed on the Surface Membrane of Activated T Cells, Immunobiol., Vol. 200, pp. 49-61 (1999).
6. Jiang, H. and Chess, L. The Specific Regulation of Immune Responses by CD8+ T Cells Restricted by the MHC Class IB Molecule, QA-1. In press Annual Review of Immunology, 2000. 18:185-216.
1. CD40L/CD40 Interactions:
A key finding of the Chess laboratory was the identification of the T cell molecule responsible for providing contact dependent help to B cells as the ligand for CD40 (CD40L). Antibodies to CD40L were created and used to show that CD40L-CD40 interactions are required for B-cell differentiation and that the CD40L-CD40 pathway is important in regulation immune responses of both T cells and B cells. During the course of these studies the cDNA encoding the CD40L was isolated and eventually in collaboration with Dr. Thomas and his colleagues the 3 dimensional structure of CD40L was deduced. Research is now focused on the mechanisms by which CD40L-CD40 interactions regulate immune responses in autoimmunity. In addition, anti-CD40L antibodies are now being used in man to treat autoimmune states and the biological and immunological effects of these antibodies are being studied.
2. CD8 regulatory studies:
Dr. Chess is interested in CD8+ T cell functions that suppress immune responses. Recent studies in collaboration with Dr. Hong Jiang support the idea that the specificity of immune regulation is mediated by specific recognition by CD8+ T cells of TCR peptides bound to MHC class I-b molecules expressed on the surface of autologous CD4+ T cells. These studies have been carried out in both murine and human species. In the mouse the class Ib molecule is Qa-1 and transfection of Qa-1 cDNA into V� expressing cells is sufficient for cells to be recognized by anti V� CD8 T cells. Dr. Chess' lab is now defining the molecular details of these important interactions and studying the potential role of these suppressive mechanisms in autoimmunity in man. This work was recently reviewed in the Annual Review of Immunology 18:185, 2000
3. The Autoimmunity Centers of Excellence (ACE):
Dr. Chess is the PI of a autoimmunity center of excellence grant (ACE) grant from the NIH. The overall objectives of the program at Columbia is primarily focussed on the evaluation of novel therapeutic approaches to five autoimmune diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS),type one diabetes mellitus (T1DM) and scleroderma. In these diseases there are ongoing basic and clinical research programs involving pathophysiologic and/or clinical immunotherapeutic studies. For example we are studying the regulatory mechanisms, including the activation of TH1 and TH2 CD4+ T cell subsets as well as those involving CD8 T-regulatory cells that are involved in the control of autoimmunity in these various diseases in man. We are also devising strategies to reduce the clonal expansion of relevant autoreactive T cells by blockade of T cell receptor signaling or interruption of the CD40 ligand-dependent pathways. In addition, T cells infiltrating inflammatory tissues express a variety of other molecules important in migration through the extracellular matrix. One of these molecules is the integrin, termed VLA-1. The first antibody to VLA-1 was prepared by Dr. Chess and has recently been shown to prevent the development of arthritis in murine models of collagen induced arthritis. Work on VLA-1 continues to define the precise immunopharmacology of the drug and its role in the pathogenesis of inflammatory disease.
Honors and Awards
1967 Alpha Omega Alpha
1979 Irma T. Herschl Foundation Scholar Award
1987 Merit Award-National Institutes of Health