1. This research plan describes experiments which are meant to investigate some mechanisms involved in the aquisition and maintenance of the repertoire of T helper cells. The strategy of these experiments is based on two assumptions: a) Idiotype-like determinants which have been detected on T and B cells with the same antigen specificities and expressed within the same immune system are a product of phenetic convergence and a major role in this convergence is played by specific T-T interactions which induce preferential expansion of certain lymphocyte clones. b) T-T interactions are an intrinsic part of the selection of the 1 region restricted T helper cell repertoire and we propose as a central focusing element of these interactions internal images of MHC determinants mimicked by T helper cell receptors. The theoretical considerations deriving from these assumptions and the corrections of our hypotheses will be assessed by experiments which will involve: enriching of helper T cells, cloning of idiotype bearing, internal image mimicking T helper cells and T cells recognizing these structures. Functional experiments will determine the role of these interactions. II. Experiments using the T cell dependent polyclonal activation of B cells will investigate the committment of in vitro generated B cells to immunoglobulin switch and the possible role of B cell differentiation antigens in isotype expression and secretion subsequent to T cell help. In this last case helper T cells raised in CBA/N mice against CBA/J B cell membrane determinants will be used. III. We will continue our trials aiming at the immortalization of functional T cell lines via transfer of oncogenes. The potentials of this approach and its significance to cancer research is obvious.
