The overall goals of this project are to characterize cells of the murine system and determine the mechanism(s) of action and interactions among these cells in antibody responses to an antigen under immune response (Ir) gene control-L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). T cells are critical for the development and regulation of immune responses; the understanding of the diversity and biological activity of T cell subsets is extensive, but little is known about T cell receptors for antigen or how regulatory T cells act. The objectives of this proposal are to identify and characterize regulatory T cell subsets in responder and nonresponder mice and (responder X nonresponder) F1 and (responder X responder)F1 mice after immunization with soluble GAT and GAT-macrophages. We have identified genetically restricted Lyt 1+, I-J- helper T cells, Lyt 1+, I-J+ suppressor-inducer and Lyt 2+, I-J+ suppressor effector T cells in (responder X nonresponder)F1 immunized with soluble GAT. Similar regulatory T cell subsets are in (responder X responder)F1 mice and are expected in parental responder and nonresponder mice. Our strategy is to establish cloned T cell lines representative of these regulatory T cell subsets and to characterize these clones by membrane antigen phenotype (Lyt 1, 2, 3; I-A; I-J; Qa 1; etc.), function and antigen-binding capacity. We plan to identify, isolate and characterize molecules in the membranes of these T cell clones which serve as recognition units or receptors for antigen and Ia restriction elements. New monoclonal serological reagents will be developed for this analysis by immunization with T cell clones. In addition, the mechanism(s) of action and interaction of the regulatory T cell clones will be determined to probe the cellular site and mechanism of expression of Ir gene function in antibody responses to GAT. These studies should lead to the identification of all essential T cell subsets involved in the regulation of antibody responses to one antigen under Ir gene control and provide insight into the nature of T cell receptors and the mechanism of Ir gene regulation of immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013915-11
Application #
3125567
Study Section
Immunobiology Study Section (IMB)
Project Start
1978-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
11
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Barnes-Jewish Hospital
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110
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Zimecki, M; Kapp, J A (1994) Presentation of antigen by B cell subsets. IV. Defective T-B cell signalling causes inability to present antigen by B cells from immunodeficient mice. Arch Immunol Ther Exp (Warsz) 42:361-7
Zimecki, M; Kapp, J A (1994) Presentation of antigen by B cell subsets. II. The role of CD5 B cells in the presentation of antigen to antigen-specific T cells. Arch Immunol Ther Exp (Warsz) 42:349-53
Zimecki, M; Kapp, J A (1994) Presentation of antigen by B cell subsets. III. Effects of interleukins on antigen presenting function and phenotype of immature B cells. Arch Immunol Ther Exp (Warsz) 42:355-9
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Lake, J P; Pierce, C W; Kennedy, J D (1991) CD8+ alpha/beta or gamma/delta T cell receptor-bearing T cells from athymic nude mice are cytolytically active in vivo. J Immunol 147:1121-6
Devens, B H; Koontz, A W; Kapp, J A et al. (1991) Involvement of two distinct regulatory T cell populations in the antigen-specific suppression of cytolytic T cell generation. J Immunol 146:1394-401
Lake, J P; Pierce, C W; Kennedy, J D (1991) T cell receptor expression by T cells that mature extrathymically in nude mice. Cell Immunol 135:259-65
Kraig, E; Kannapell, C C; Zborowski, K A et al. (1990) Sequence of the TCR beta chain gene used by a T cell clone specific for the synthetic polymer, GAT. Nucleic Acids Res 18:5881

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