The molecular definition of the T cell receptor (TCR) has revealed the fact that there are two different TCR isotypes, which are expressed on two mutually exclusive sets of T cells, termed T gamma delta and T alpha beta cells. However, recent evidence obtained with TCR isotype specific mAb in the chicken has suggested that this is not the full extent of TCR isotope heterogeneity. We have demonstrated the existence of two novel types of chicken CD3+ cells that do not express either the gamma delta or alpha beta TCR isotype. This proposal focuses on the lineal relationships between these different CD3+ cells and their functional roles. The TCRO cells develop early in ontogeny and contain cytoplasmic, but no surface CD3. Preliminary experiments have suggested that these cells arise extrathymically and are not precursors for TCR1+ (gamma delta) or TCR2+ (alpha beta) cells. Cells with a similar phenotype have been observed in human fetal liver and bone marrow, and our preliminary results suggest a similar cell in murine fetal liver. Whether cells with this phylogenetically conserved phenotype represent cells with homologous function, however, is not clear. Studies are proposed to investigate the ability of TCRO cells to differentiate into cells with surface CD3/TCR complexes and to determine the functional activities of these cells if they f&il to develop into conventional T cells. The TCR3 cells develop late in ontogeny and express surface CD3 in association with a novel heterodimer. These cells first appear after hatching and comprise approximately 15% of all peripheral blood CD3+ cells in birds 6 months old. At this time, TCR3 cells are 90% CD4+ and 10% CD8+, with no double positive or negative cells seen. Although TCR3 cells develop late in ontogeny, neonatal thymectomy does not alter the relative frequency of TCR3 cells. By combining embryonic treatment with TCR2 mAb and neonatal thymectomy, birds which contain predominantly TCR3 cells can be prepared. Studies are proposed to define the frequency and histologic distribution of TCR3 cells and to characterize their function both in vitro and in vivo. Finally, experiments are proposed to define the kinetics of thymic maturation of TCR1+ and TCR2+ cells by using BrdU labeling and immunofluorescence analysis.
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