Abstract

The study of the activation and immune interactions of developing and mature T lymphocytes has been a major concern of our laboratory. This project proposes to identify T cell surface structures that are important for these funcitons through the development of monoclonal antibodies. These antibodies will be used in conjunction with both normal and transformed (hybridomas and lymphomas), T cell clones and heterogeneous cell populations. Preliminary studies have identified a novel, functionally important epitope on the surface of murine T lymphocytes. This project will develop monoclonal antibodies to novel T cell surface determinants and address the following aspects of these molecules: 1). The functional role of these molecules in cellular immune interactions and T lymphocyte activation. 2). The phenotypic and functional heterogeneity of normal and malignant T cells. 3). The expression and functional role of these determinants during T cell development. 4). The genetics and biochemical structure of these molecules.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022397-02
Application #
3133415
Study Section
Immunobiology Study Section (IMB)
Project Start
1985-09-30
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Rock, K L; Reiser, H; Bamezai, A et al. (1989) The LY-6 locus: a multigene family encoding phosphatidylinositol-anchored membrane proteins concerned with T-cell activation. Immunol Rev 111:195-224
Sy, M S; Wang, P T; Ju, S T et al. (1988) Abnormal T cells from MRL/Mp-lpr/lpr mice do not respond to anti-T-cell-receptor antibody or tumor promoter and calcium ionophore A23187 despite the presence of the T-cell-receptor complex and protein kinase c. Cell Immunol 113:82-94
Williams, W W; Falo Jr, L D; Lu, C Y et al. (1988) Effects of in vivo monoclonal anti-I-A antibody treatment in neonatal mice on intrathymic and peripheral class II antigen expression. Cell Immunol 111:126-38
Reiser, H; Yeh, E T; Coligan, J et al. (1988) Structure and function of the TAP protein and related Ly-6-linked molecules. Year Immunol 3:80-8
Yeh, E T; Reiser, H; Bamezai, A et al. (1988) TAP transcription and phosphatidylinositol linkage mutants are defective in activation through the T cell receptor. Cell 52:665-74
Bamezai, A; Reiser, H; Rock, K L (1988) T cell receptor/CD3 negative variants are unresponsive to stimulation through the Ly-6 encoded molecule, TAP. J Immunol 141:1423-8
Reiser, H; Coligan, J; Benacerraf, B et al. (1987) Biosynthesis, glycosylation, and partial N-terminal amino acid sequence of the T-cell-activating protein TAP. Proc Natl Acad Sci U S A 84:3370-4
Yeh, E T; Reiser, H; Daley, J et al. (1987) Stimulation of T cells via the TAP molecule, a member in a family of activating proteins encoded in the Ly-6 locus. J Immunol 138:91-7
Weston, K M; Yeh, E T; Sy, M S (1987) Autoreactivity accelerates the development of autoimmunity and lymphoproliferation in MRL/Mp-lpr/lpr mice. J Immunol 139:734-42
Rock, K L; Yeh, E T; Gramm, C F et al. (1986) TAP, a novel T cell-activating protein involved in the stimulation of MHC-restricted T lymphocytes. J Exp Med 163:315-33

Showing the most recent 10 out of 14 publications