T lymphocytes divided and differentiate when they receive an appropriate activation signal. This signal can be provided by a clonally-distributed, specific antigen receptor, or through certain broadly distributed by cell membrane structures. Molecular biological and in vitro cell celture techniques have been used to investigate the expression of the genes encoding these activation structures, and to study the relationship between structure and function. Direct evidence was obtained that the AlphaBeta heterodimer identified on T cells by anti-clonotypic antibodies completely determines the specificity of a given T lymphocyte. This was accomplished by DNA-mediated gene transfer of Alpha and Beta genes into human T cells, which acquired the specificity of the mouse T cell donating the genes. Similar gene transfer experiments using the Thy-1 gene suggest that the activation function of this non-clonally distributed T cell marker may be related to the T3-dependent triggering mechanism used by the AlphaBeta receptor. Ontogenetic studies were carried out using in situ hybridization methods involving specific radioactive RNA probes. These experiments revealed the ordered expression of T cell receptor Gamma, Beta, then Alpha genes druing fetal development of T cells in the thymus. They also showed the acquisition and loss of high levels of interleukin-2 mRNA and interleukin-2 receptor mRNA in developing T cell population. RNA and DNA analysis of an unusual Thy-1 positive cell from the skin revealed that these cells expressed T cell receptor genes in paterns resembling these different stages of thymic T cell development. These studies will enhance our knowledge of which cell membrane molecules are involved in triggering T cells to exert regulatory and effector function, and our understanding of the structural basis for specific T cell responses to antigen.
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