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.
| 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 |
| 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 |
| Marsden, Vanessa S; Kappler, John W; Marrack, Philippa C (2006) Homeostasis of the memory T cell pool. Int Arch Allergy Immunol 139:63-74 |
| 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 |
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