The projects proposed relate to molecular structures and regulation in the immune system. Individual hybridoma products (HP's), expressing the major idiotype of anti-phenylarsonate (anti-Ar) antibodies of strain A mice, bear unique idiotypic determinants, not found on other HP's tested but present in strain A immune serum. We will study the ontogeny of a number of such determinants to obtain additional information as to whether the appearance of particular clonotypes is genetically programmed. In collaborative research we will determine whether auto-anti-id antibodies appear during the early immune response to the Ar hapten (as is the case for TNP), and interfere with plaque formations. The use of a well-defined idiotypic system should facilitate new approaches toward understanding this regulatory system. We will attempt to determine whether regulatory T cells are formed in response to private idiotypic determinants; whether regulatory T cells are formed in response to private idiotypic determinants; i.e. whether idiotypic regulation is restricted to the major idiotypes. The experiments will be done by using idiotype-conjugated syngeneic cells for anti-idiotypic antibodies specific for private determinants. The extent of the effector T cell repertoire will be explored by determining whether such private idiotypic determinants are present on T cells responsible for delayed-type hypersensitivity. It is known that idiotype-specific helper T cells are required for substantial expression of the major idiotype. We will ascertain whether such helper cells are also needed for expression of a minor idiotype. This addresses the general question of the need for antiidiotypic help in the expression of various clonotypes. Work of others on the effects of suppressor T cells on secretion of antibody by B cell tumors will be extended by using T cells with idiotypic and antiidiotypic receptors. Efforts will be made to crystallize Fab fragments, for use in crystallography, of a number of anti-Ar HP's that carry the major idiotype. We will provide hybridomas to be used in a study of the genes controlling the T cell receptor and will attempt to obtain continuous T cell lines for use in those experiments.
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| Hathcock, K S; Gurish, M F; Nisonoff, A et al. (1986) Influence of helper T cells on the expression of a murine intrastrain crossreactive idiotype. Proc Natl Acad Sci U S A 83:155-9 |
| Robbins, P F; Rosen, E M; Haba, S et al. (1986) Relationship of VH and VL genes encoding three idiotypic families of anti-p-azobenzenearsonate antibodies. Proc Natl Acad Sci U S A 83:1050-4 |
| Haba, S; Nisonoff, A (1985) Quantitation of IgE antibodies by radioimmunoassay in the presence of high concentrations of non-IgE antibodies of the same specificity. J Immunol Methods 85:39-52 |
