The long-term objective of this research is to elucidate the biological functions of the self-reactive T cells that recognize the idiotopes (Id) of immunoglobulin molecules. These Id- specific T cells (TId) are perceived as the major regulators of antibody response to bacterial antigens and, perhaps, as immunosurveillance cells for the Id-positive lymphomas. The proposed project was fueled by a new method for establishment of stable T cell lines/clones that specifically recognize the idiotopes of the T15 immunoglobulin. The T15-specific TId lines have been derived using syngeneic B cell lymphoma transfected with the T15 genes. Since the T15 molecule is the prototype of the antibody that protects mice against S. pneumonial (Pn) infection, the availability of T15-specific TId opens the way to fully elucidate the regulation of T15Id + B cell response to Pn. Moreover, the receptor specificity and properties of autologous TId can now be formally studied.
The first aim i s to determine the TcR structure and the fine specificity of TId lines/clones and to elucidate the response of these T cells to various forms of Id molecules, both soluble and cell-bound. Secondly, the regulation of antibody response to Pn by the TId lines/clones will be studied in vitro, in order to determine the mechanisms by which the TId stimulate and/or suppress the functions of the Id+, Pn-responsive B lymphocytes. The collaboration of TId, with antigen-specific T helper clones in regulation of antibody response will also be studied, using lymphocyte cultures immunized with various forms of the Pn antigen.
The third aim i s to determine the biological significance of TId in vivo using (a) adoptive transfer of TId lines/clones into nude mice, (b) measurements of the frequency and localization of TId in normal and T15-transgenic mice, and (c) deletion of various TId subsets, in situ, followed by Pn immunization. The last aim is to explore the cytostatic (growth-inhibitory) effects of TId lines/clones on Id+ B cell lymphomas in vitro and the protection of mice against the transplanted tumors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI023900-04
Application #
3136435
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1990-01-01
Project End
1992-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Yamaguchi, M; Sayama, K; Yano, K et al. (1999) IgE enhances Fc epsilon receptor I expression and IgE-dependent release of histamine and lipid mediators from human umbilical cord blood-derived mast cells: synergistic effect of IL-4 and IgE on human mast cell Fc epsilon receptor I expression and mediato J Immunol 162:5455-65
Maurer, M; Echtenacher, B; Hultner, L et al. (1998) The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells. J Exp Med 188:2343-8
Nicoletti, C; Cerny, J (1992) A study of autologous anti-idiotypic antibody-forming cells in mice of different ages and genetic backgrounds. Cell Immunol 144:332-46
Striebich, C C; Miceli, R M; Schulze, D H et al. (1990) Antigen-binding repertoire and Ig H chain gene usage among B cell hybridomas from normal and autoimmune mice. J Immunol 144:1857-65
Kaushik, A; Schulze, D H; Bonilla, F A et al. (1990) Stochastic pairing of heavy-chain and kappa light-chain variable gene families occurs in polyclonally activated B cells. Proc Natl Acad Sci U S A 87:4932-6
Strickland, F M; Cronkhite, R I; Cerny, J (1989) Regulation of idiotype expression. II. The phenotypic diversity of T15 idiotype-bearing antibody to phosphorylcholine in response to T-dependent and T-independent antigens. Immunology 67:8-15
Strickland, F M; Cerny, J; Currier, P et al. (1989) Restricted idiotypic profile of anti-phosphorylcholine antibodies induced by carrier-specific helper T cell clones. Eur J Immunol 19:971-6
Kelsoe, G; Miceli, R; Cerny, J et al. (1989) Mapping of antibody specificities to VH gene families. Immunogenetics 29:288-96
Cronkhite, R; Strickland, F; Cerny, J (1988) Regulation of idiotope expression. III. H-2 influences the magnitude and the idiotypy of a T-independent antibody response in mice of certain genetic backgrounds. J Immunol 141:921-5
Cerny, J; Smith, J S; Webb, C et al. (1988) Properties of anti-idiotypic T cell lines propagated with syngeneic B lymphocytes. I. T cells bind intact idiotypes and discriminate between the somatic idiotypic variants in a manner similar to the anti-idiotopic antibodies. J Immunol 141:3718-25