ANTIBODY FORMATION BY LYMPHOID CELLS

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Immune responses involving T lymphocytes are of major importance in determining the fate of organ grafts, the outcome of many virus infections, and probably the response to tumors as well. T lymphocytes react with antigens in each of these situations through antigen-specific cell surface receptors. Although a considerable body of evidence indicates that the T cell receptor shares idiotypic determinants with those found on immunoglobolin and that there is genetic linkage between the T cell receptor and the immunoglobulin heavy chain allotype, this important cell receptor has remained elusive. With the development of cloned T cells and antibody-producing hybridoma technology, it is now possible to obtain homogeneous T cells and monoclonal antibodies. We will use these materials to characterize the antigen receptor of cytolytic T lymphocytes (CTL). We have obtained a "clone-specific" monoclonal antibody, and we will develop additional monoclonal "clone-specific" antibodies which inhibit the antigen-related functions of cloned CTL. Such antibodies are likely candidates for antibodies reactive with the T cell receptor for antigen. We also will develop monoclonal antibodies reactive with CTL alloantigens ("IgT-CCTL") which are linked with immunoglobulin (Ig) heavy chain allotypes. Such antibodies are likely candidates for antibodies reactive with "constant region" markers on the T cell receptor. The "clone-specific" and "IgT-CCTL" antibodies and the CTL with which they react will be used in collaborative studies with Dr. Susumu Tonegawa to identify and characterize genes coding for the antigen receptors of cytolytic T cells. We also will try to determine whether CTL and antibodies reactive with the same alloantigenic epitope bear the same idiotype. The ultimate objectives of the proposed studies are to gain a better understanding of the functional characteristics of the T cell receptor for antigen and to develop more specific, rational, and effective means to manipulate specific immune responses. Although mice are being used in these studies, we feel that the information obtained may be applicable ultimately in human situations.