Research: Twenty-three new monoclonal antibodies (mAb) have been made which recognize the human T cell receptor. Different examples of these mAb are directed against: 1) all human T cell receptors; 2) one subset of T cell receptors on normal T cells; and 3) clonotypic epitopes on the HPB-ALL receptor molecule. These mAb will be used: 1) to isolate T cell receptors for biochemical analyses; 2) to identify T cell receptor epitopes which may be allotypic or represent conformational states; and 3) to isolate receptors from peripheral blood T cells of rheumatoid arthritis patients in order to immunize mice. MAb will be made from mice producing antibodies to rheumatoid arthritis T cell receptors in order to identify additional subsets of T cell receptors (other than those represented by the HPB-ALL receptor) and to investigate whether cross-reactive T cell receptor idiotypes (clonotypes) occur in rheumatoid arthritis. Cross-reactive idiotypes and T cell receptor subsets which are identified will be biochemically characterized. In addition, structural studies using chemical cross-linking will be performed to further delineate the arrangement of the 5 chains of the T cell receptor molecule: 1) on the cell surface; 2) within the plasma membrane; and 3) on the cytoplasmic face of the membrane. These studies may contribute to our understanding of the structure-function relationships for the receptor. For example, changes in chain association or conformation of the receptor which may occur upon T cell activation by antigen will be investigated. Candidate: The applicant is trained in clinical medicine having served as Chief Resident in Medicine at Vanderbilt University Hospital and as a clinical fellow in rheumatology at U.C.L.A. Research training began at the U.C.L.A.-affiliated Wadsworth Veterans Administration Hospital and has continued during the past 2 years with Dr. Jack Strominger, Professor of Biochemistry, Harvard University and Dana-Farber Cancer Institute. The applicant has recently been appointed to Asst. Prof. in Medicine at Harvard Medical School. Environment: The sponsor's laboratory is expert in biochemistry and molecular biology and the Rheumatology Division at Brigham and Women's Hospital offers an extensive clinical experience.
| Hochstenbach, F; Parker, C; McLean, J et al. (1988) Characterization of a third form of the human T cell receptor gamma/delta. J Exp Med 168:761-76 |
