The thymus leukemia (TL) molecule is an oncofetal antigen encoded by a class I gene in the mouse major histocompatibility complex (MHC). The goal of the proposed experiments is to gain insight into the possible function(s) of the TL molecule. A series of experiments will compare TL to a transplantation antigen, to determine if TL can interact with CD8, if it can present antigen, and if it can educate a repertoire of TL-restricted T cells. An attempt will be made to demonstrate if TL presents antigen to intestinal epithelial lymphocytes. To determine if TL has any role in either T cell proliferation or maturation, two types of transgenic mice will be characterized. Both types have abnormally high expression of TL on either their mature T cells, or on all of their cells. Monoclonal antibodies will be used to monitor the number and maturity of T cells in these animals, and functional assays on these cells will be carried out. Cell transfer experiments will be performed to determine if the TL+ fraction of fetal liver cells is comprised of cells committed to the T cell lineage. Furthermore, the effect of crosslinking surface TL on Ca+2 flux, proliferation, Il-2 synthesis and the activation of protein kinases will be explored. The function of the MHC class Ib genes has been an enigma. TL is the product of a representative MHC class Ib gene that is of particular interest on account of its expression by transformed and immature cells. The proposed experiments utilize a battery of modern techniques to explore the possible role of the TL molecule, whether it be in immune surveillance or in lymphocyte differentiation. By extension, these data should contribute insight into the function of other members of the potentially important group of MHC class Ib molecules.
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