We are studying gamma/delta T cell antigen receptors (TCR) and lymphocyte co-receptors with the purpose of understanding their role in the activation of an immune response. Our goal is to analyze these proteins biochemically and structurally. To do so requires that we produce sufficient amounts of protein for study and that we characterize the recombinant proteins for their appropriate functionality. Further study of their binding to ligands and of their three-dimensional structure by X-ray crystallography should lead to insights as to how these proteins function in the immune system. Unlike alpha/beta T cell receptors, which recognize peptide antigens bound to major histocompatibility complex molecules, gamma/delta TCRs can directly recognize antigens as intact proteins or non-peptidic compounds. About 5% of all primate peripheral blood T cells bear gamma/delta TCRs, most of which recognize non-peptidic phosphorylated antigens. In earlier work, we have determined the structure of a human gamma/delta TCR isolated from a T cell clone that is activated by phosphoantigens. We are now studying the binding of non-peptidic phosphorylated antigens to the gamma/delta TCR using crystallographic, biochemical, and biophysical techniques. We are also studying the structure and function of several lymphocyte co-receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000835-09
Application #
7303785
Study Section
(SBS)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lin, David Yin-Wei; Tanaka, Yoshimasa; Iwasaki, Masashi et al. (2008) The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. Proc Natl Acad Sci U S A 105:3011-6
Terawaki, Seigo; Tanaka, Yoshimasa; Nagakura, Tomokazu et al. (2007) Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function. Int Immunol 19:881-90
Garboczi, David N (2005) Structural biology. ""D"" is not for diversity. Science 308:209-10
Allison, Timothy J; Garboczi, David N (2002) Structure of gammadelta T cell receptors and their recognition of non-peptide antigens. Mol Immunol 38:1051-61
Allison, T J; Winter, C C; Fournie, J J et al. (2001) Structure of a human gammadelta T-cell antigen receptor. Nature 411:820-4
Garboczi, D N; Biddison, W E (1999) Shapes of MHC restriction. Immunity 10:1-7