This program will deal broadly with cellular and molecular aspects of antigen recognition by thymus-derived lymphocytes (T cells) and with T-cell regulation of two immune responses: induction of cytotoxic T lymphocytes and diversification of variable domains of antibodies during primary antibody responses. Antigen recognition will be studied by preparing antisera by xenogeneic, allogeneic, and isogeneic immunization using cloned T cells as immunogens. Antisera will be evaluated for their ability to block in a clone-specific manner the function of the T cells used as immunogens. Active antisera also will be used to immunoprecipitate components in extracts of ?125?I-labeled cloned T cells in an effort to detect and characterize any molecules on the T-cell surface that may be involved in antigen recognition. In other studies of cytotoxic T lymphocytes, cell surface """"""""effector"""""""" molecules that may be involved in the lysis of target cells will be identified and tested to see if they have any of several obvious enzymatic activities (amino acid esterase, etc.). (LB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA028900-09
Application #
3093278
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1981-01-01
Project End
1990-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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Kappes, D J; Browne, C P; Tonegawa, S (1991) Identification of a T-cell-specific enhancer at the locus encoding T-cell antigen receptor gamma chain. Proc Natl Acad Sci U S A 88:2204-8
Spencer, D M; Hsiang, Y H; Goldman, J P et al. (1991) Identification of a T-cell-specific transcriptional enhancer located 3' of C gamma 1 in the murine T-cell receptor gamma locus. Proc Natl Acad Sci U S A 88:800-4
Van Kaer, L; Wu, M; Ichikawa, Y et al. (1991) Recognition of MHC TL gene products by gamma delta T cells. Immunol Rev 120:89-115
Kamradt, T; Soloway, P D; Perkins, D L et al. (1991) Pertussis toxin prevents the induction of peripheral T cell anergy and enhances the T cell response to an encephalitogenic peptide of myelin basic protein. J Immunol 147:3296-302
Bonneville, M; Itohara, S; Krecko, E G et al. (1990) Transgenic mice demonstrate that epithelial homing of gamma/delta T cells is determined by cell lineages independent of T cell receptor specificity. J Exp Med 171:1015-26
Lai, M Z; Jang, Y J; Chen, L K et al. (1990) Restricted V-(D)-J junctional regions in the T cell response to lambda-repressor. Identification of residues critical for antigen recognition. J Immunol 144:4851-6
Ito, K; Van Kaer, L; Bonneville, M et al. (1990) Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor. Cell 62:549-61
Liao, N S; Maltzman, J; Raulet, D H (1990) Expression of the V beta 5.1 gene by murine peripheral T cells is controlled by MHC genes and skewed to the CD8+ subset. J Immunol 144:844-8
Farr, A; Hosier, S; Nelson, A et al. (1990) Distribution of thymocytes expressing gamma delta receptors in the murine thymus during development. J Immunol 144:492-8

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