Stanley Nathenson, MD

Professor, Departments of Cell Biology and Microbiology & Immunology Chanin Bldg., Room 407 718 430-2226 nathenso@aecom.yu.edu Complete list of publications

Research interests How do T cells see antigens? The two major arms of the immune response system in mammals are the antibody system controlled by B cells, and the cell mediated immune system controlled by T cells. The antibody system uses rearranged and somatically mutated genes to express proteins with binding specificity for foreign antigens. The cell mediated immune system utilizes two components: (1) the class I major histocompatibility complex (MHC) molecules (to present antigens) and (2) the T cell receptors (TCR) found on the cytolytic or helper T cells to recognize the antigens presented by the MHC antigen presenting molecules on the cell surface. My research interests are on the structural basis for peptide antigen presentation by MHC molecules, as well as on the structural features of T cell receptors important for recognizing these antigens. The class I MHC proteins bind foreign antigens in the form of peptides (short peptides 8 to 10 amino acids long). Such peptides are processed fragments derived from the proteins of foreign viruses and other pathogens which invade the cells of the body. Biochemical studies using in vitro complex formation of MHC/peptide are being used to evaluate the precise mechanism of peptide binding and determine the structural rules which govern the selection and binding of such peptides to the MHC molecule. To define the features important for recognizing the peptide and the MHC complex by the TCR, T cells specifically recognizing variant peptide antigens are being raised, and their TCRs sequenced. Using a model system in which transgenic mice express one of the two chains of the TCR we are able to precisely focus on the structure of the TCR beta chain. Such an approach gives us an analytical tool to precisely define the amino acid residues which interact with the peptide. Structural analysis of the three dimensional level will also be used o define TCR/peptide/MHC interaction in atomic detail.

Recent publications Franco A, et al. Fine specificity and MHC restriction of trinitrophenyl-specific CTL. J Immunol. 1999 Mar 15;162(6):3388-94. Goyarts EC, et al. Point mutations in the beta chain CDR3 can alter the T cell receptor recognition pattern on an MHC class I/peptide complex over a broad interface area. Mol Immunol. 1998 Jul;35(10):593-607. Ono T, et al. Alterations in TCR-MHC contacts subsequent to cross-recognition of class I MHC and singly substituted peptide variants. J Immunol. 1998 Nov 15;161(10):5454-63. DiLorenzo TP, et al. Major histocompatibility complex class I-restricted T cells are required for all but the end stages of diabetes development in nonobese diabetic mice and use a prevalent T cell receptor alpha chain gene rearrangement. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12538-43. Wang F, et al. On defining the rules for interactions between the T cell receptor and its ligand: a critical role for a specific amino acid residue of the T cell receptor beta chain. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5217-22.

Stanley Nathenson: Research interests Faculty research at a glance Birshtein | Bouhassira | Edelmann | Fyodorov | Keogh | Kielian | Kitsis | Nathenson | Query Scharff | Schildkraut | Shafritz | Singer | Skoultchi | Stanley | Steidl |Warner | Ye   Home