By means of cell transfers between allotype(Igh)-congenic mouse strains, we have shown Igha mice to contain T cells that can prevent both the production of a specific B cell allotype (Igh-1b) in normal and in athymic Ighb mice - and the growth of an established line of Igh-1b-producing tumor cells. We have referred to these cytotoxic (c) or suppressor (s) T cells as Igh-1b Tcs cells. Recently, we succeeded in adapting long-term, cultured lines of Igha T cells that specifically kill Igh-1b tumor cells in vitro; several of these Igh-1b Tc cell lines also have been shown capable of suppressing Igh-1b production in vivo. We propose to use clones of Igh-1b Tc cells as a model system for investigating how T cells can recognize and control the proliferation of a specific population of B cells. We have evidence this involves a T cell receptor specific for Igh-1b; therefore, we are particularly interested in characterizing this receptor and the gene(s) responsible. To do this we will take as a given that antigen-specific receptors on both T and B cells are encoded (in part) by Heavy chain variable region (VH) genes. Thus, select B cell hybridomas that produce receptors (antibodies) specific for Igh-1b will be used for the construction of relevant cDNA probes. Probes will be made specific for VH genes and used to examine clones of Igh-1b Tc cells that express VH idiotypes identical or similar to those of the B cell hybridomas. Igh-1b Tc cell lines lacking the appropriate VH idiotype along with unrelated cell lines of T and B tumors will serve as negative controls.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013323-10
Application #
3125425
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1976-05-01
Project End
1986-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Institute for Cancer Research
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
Chang, Y; Bosma, G C; Bosma, M J (1995) Development of B cells in scid mice with immunoglobulin transgenes: implications for the control of V(D)J recombination. Immunity 2:607-16
Nakajima, P B; Menetski, J P; Roth, D B et al. (1995) V-D-J rearrangements at the T cell receptor delta locus in mouse thymocytes of the alpha beta lineage. Immunity 3:609-21
Fish, S M; Bosma, M J (1994) Abnormal deletions in the T-cell receptor delta locus of mouse thymocytes. Mol Cell Biol 14:4455-64
Kotloff, D B; Bosma, M J; Ruetsch, N R (1993) Scid mouse Pre-B cells with intracellular mu chains: analysis of recombinase activity and IgH gene rearrangements. Int Immunol 5:383-91
Kotloff, D B; Bosma, M J; Ruetsch, N R (1993) V(D)J recombination in peritoneal B cells of leaky scid mice. J Exp Med 178:1981-94
Roth, D B; Menetski, J P; Nakajima, P B et al. (1992) V(D)J recombination: broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes. Cell 70:983-91
Roth, D B; Nakajima, P B; Menetski, J P et al. (1992) Double-strand breaks associated with V(D)J recombination at the TCR delta locus in murine thymocytes. Curr Top Microbiol Immunol 182:115-24
Bosma, M J (1992) B and T cell leakiness in the scid mouse mutant. Immunodefic Rev 3:261-76
Roth, D B; Nakajima, P B; Menetski, J P et al. (1992) V(D)J recombination in mouse thymocytes: double-strand breaks near T cell receptor delta rearrangement signals. Cell 69:41-53
Carroll, A M; Bosma, M J (1991) T-lymphocyte development in scid mice is arrested shortly after the initiation of T-cell receptor delta gene recombination. Genes Dev 5:1357-66

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