Abstract

The aims of this proposal are to understand in detail the means whereby T cells help B cells respond to antigen. We are particularly interested in two processes which occur; first, the events which initiate B cell response and secondly, the effects on B cells of the lymphokine B cell stimulating factor-1 (BSF1). Although lymphokines alone can drive the responses of B cells to some antigens responses of B cells to many antigens, particularly those born on proteins, require the presence of carrier-specific T cells as well as lymphokines. These T cells appear to be involved chiefly at the beginning of the B cell response. they may be acting by secreting some hitherto undiscovered lymphokine or by direct contact of their own membrane proteins with ligands on T or B cells and/or isolated membrane proteins, we plan to investigate which of these possibilities is correct. Membrane components to be studied will include the T cell receptor, L3T4, LFA-1 and Class II molecules. For example, we will isolate receptors from a particular helper T cell hybridoma and test by various strategies whether these receptors bind antigen plus MHC. These receptors will be used in liposomes or after transfer to another T cell hybridoma to test for antigen-specific helper activity. BSF1 has a number of effects on B cells. It induces Ia synthesis in resting cells, and stimulates proliferation of sub-maximally activated B cells. We plan to isolate the receptor for BSF1 on B cells, and study in detail the inductive effects of this lymphokine no resting cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37AI017134-08
Application #
3480903
Study Section
Immunobiology Study Section (IMB)
Project Start
1979-12-01
Project End
1991-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
National Jewish Health
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206

  Publications

Clayton, Gina M; Wang, Yang; Crawford, Frances et al. (2014) Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity. Cell 158:132-42
Clambey, Eric T; Collins, Bernard; Young, Mary H et al. (2013) The Ikaros transcription factor regulates responsiveness to IL-12 and expression of IL-2 receptor alpha in mature, activated CD8 T cells. PLoS One 8:e57435
Dai, Shaodong; Murphy, Guinevere A; Crawford, Frances et al. (2010) Crystal structure of HLA-DP2 and implications for chronic beryllium disease. Proc Natl Acad Sci U S A 107:7425-30
Stadinski, Brian D; Zhang, Li; Crawford, Frances et al. (2010) Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register. Proc Natl Acad Sci U S A 107:10978-83
Wang, Yibing; Becker, Dean; Vass, Tibor et al. (2009) A conserved CXXC motif in CD3epsilon is critical for T cell development and TCR signaling. PLoS Biol 7:e1000253
Rubtsova, Kira; Scott-Browne, James P; Crawford, Frances et al. (2009) Many different Vbeta CDR3s can reveal the inherent MHC reactivity of germline-encoded TCR V regions. Proc Natl Acad Sci U S A 106:7951-6
Willis, Richard A; Kappler, John W; Marrack, Philippa C (2006) CD8 T cell competition for dendritic cells in vivo is an early event in activation. Proc Natl Acad Sci U S A 103:12063-8
Robertson, Jennifer M; MacLeod, Megan; Marsden, Vanessa S et al. (2006) Not all CD4+ memory T cells are long lived. Immunol Rev 211:49-57
Zhu, Yanan; Liu, Xinqi; Hildeman, David et al. (2006) Bax does not have to adopt its final form to drive T cell death. J Exp Med 203:1147-52
Huseby, Eric S; Crawford, Frances; White, Janice et al. (2006) Interface-disrupting amino acids establish specificity between T cell receptors and complexes of major histocompatibility complex and peptide. Nat Immunol 7:1191-9

Showing the most recent 10 out of 74 publications