The main aim of this proposal is to seek information on the response of T lymphocytes to Mls determinants; these determinants are expressed on a subset of B cells and are strongly stimulatory for T cells. We are primarily interested in two particular questions: (1) Are the receptors used by T cells to recognize Mls determinants the same or different to the receptors for conventional antigens? We have preliminary evidence that anti-Mls receptors might indeed be different. This evidence stems from the finding that T hybridomas with dual specificity for Mls and conventional antigens can lose reactivity for one set of antigens but not the other. Using a variety of techniques, including examination of T hybridomas at the DNA level and production of T-cell-receptor-specific monoclonal antibodies, we seek direct evidence that a unique and separate set of receptors control the T-cell response to Mls determinants. (2) How do T cells """"""""see"""""""" Mls determinants on B cells, particularly on resting small B cells. We propose to test the idea that, for B cells to present Mls determinants, the cells require prior activation. We will examine whether exposing B cells to treatments that inhibit cell activation concommitantly inhibits presentation of Mls determinants. We also will address the question of the role of Ia determinants in Mls-specific responses. (AG)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041993-03
Application #
3182657
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037
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Hayden, K A; Tough, D F; Webb, S R (1996) In vivo response of mature T cells to Mlsa antigens. Long-term progeny of dividing cells include cells with a naive phenotype. J Immunol 156:48-55
Sprent, J; Webb, S R (1995) Intrathymic and extrathymic clonal deletion of T cells. Curr Opin Immunol 7:196-205

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