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
Camacho, S A; Heath, W R; Carbone, F R et al. (2001) A key role for ICAM-1 in generating effector cells mediating inflammatory responses. Nat Immunol 2:523-9
Ragazzo, J L; Ozaki, M E; Karlsson, L et al. (2001) Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naive CD4+ T cells. Proc Natl Acad Sci U S A 98:241-6
Ozaki, M E; Webb, S R (2000) Controlling mature CD4+ T cell responses. Immunol Res 21:345-55
Ozaki, M E; Coren, B A; Huynh, T N et al. (1999) CD4+ T cell responses to CD40-deficient APCs: defects in proliferation and negative selection apply only with B cells as APCs. J Immunol 163:5250-6
Luksch, C R; Winqvist, O; Ozaki, M E et al. (1999) Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells. Proc Natl Acad Sci U S A 96:3023-8
Ozaki, M E; Karlsson, L; Peterson, P A et al. (1997) Antigen specificity of dual reactive T hybridomas determines the requirement for CD40 ligand-CD40 interactions. J Immunol 159:214-21
Hartwig, U F; Karlsson, L; Peterson, P A et al. (1997) CD40 and IL-4 regulate murine CD27L expression. J Immunol 159:6000-8
O'Rourke, A M; Webb, S R (1997) Cross talk between T and B cells generates B antigen-presenting cells able to induce inositol phosphate production in T cells responding to Mls(a) superantigens. Eur J Immunol 27:3253-8
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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