This proposal analyzes the relationship between the T cell receptor alpha/beta molecules and the antigen binding chain of soluble suppressor T cell derived factors. We propose several approaches to establish a relationship between components of the conventional CD3-TcR complex and the antigen specific regulatory factors released by suppressor T cell hybridomas. Data presented in the application demonstrate the use of TcR expression variants' and TcR-alpha transfection to directly address this issue. Additional experiments are proposed to extend these observations and to evaluate if TsF with new antigen specificity can be engineered. Additional studies are aimed at comparing and defining the chains associated with inducer (TsF1) and effector (TsF3) suppressor factors. These studies will test the hypothesis that TsF consists of a heterodimer composed of TcR-alpha plus either of two distinct nonspecific suppressive molecules which may express phospholipase inhibitory activity. Specific experiments involve heterologous transfections and bioassays to determine the relationships between various serological determinants associated with TsF bioactivity. Finally, we propose to biochemically isolate and characterize TsF. The combined aims should provide a better understanding of suppressor T cells and their products. The phenomenon of T cell mediated suppression may play a central role in the homeostatic mechanisms which normally regulate immune responses. Thus, this proposal may have direct application for control of autoimmunity and cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA056057-02
Application #
3200537
Study Section
Experimental Immunology Study Section (EI)
Project Start
1992-09-04
Project End
1996-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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Luo, Y; Laning, J; Hayashi, M et al. (1994) Serologic analysis of the mouse beta chemokine JE/monocyte chemoattractant protein-1. J Immunol 153:3708-16
Luo, Y; Laning, J; Devi, S et al. (1994) Biologic activities of the murine beta-chemokine TCA3. J Immunol 153:4616-24
Laning, J; Kawasaki, H; Tanaka, E et al. (1994) Inhibition of in vivo tumor growth by the beta chemokine, TCA3. J Immunol 153:4625-35

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