Soluble extracts of many mammalian tissues, including lung and spleen, contain Beta-galactoside binding lectins. Three were recently purified from rat lung with subunit Mrs 14,500, 18,000 and 29,000 (RL-14.5, RL-18 and Rl-29) and two were purified from human lung (HL-14 and HL-29). Previous work suggests that these lectins function at the cell surface or extracellularly by interacting with specific glycoconjugates. Our goal is to accumulate structural and functional information about these lectins which will lead to an understanding of their biological roles. THe biological studies will be done with lymphocytes because they have many practical advantages and contain both RL-14.5 and receptors for this lectin. These studies will contribute to a general understanding of endogenous lectin functions in the many tissues which contain them. We propose to: a. Identify relative binding of these endogenous lectins to a large panel of known mammalian glycoconjugates, to define their active sites and potential competitive interactions. b. Identify lymphocyte glycoproteins and glycolipids which act as receptors for these endogenous lectins, as judged by their binding properties. c. Examine the biological effects of these lectins. Initially we will continue our studies which show that exogenous RL-14.5 activates B or T lymphocytes (but only in conjunction with specific growth factors). Then we will determine if this endogenous lectin (which we find in virtually all B and most T lymphocytes) is secreted and involved in the lymphocyte activation which normally results from specific cell-cell interactions. d. Clone the genes for HL-14, HL-29 and related mammalian lectins. The genes will be used to deduce amino acid sequences; to determine if there are multiple forms of the lectins under different developmental control; and for functional studies using lymphocyte cell lines transformed with anti-sense DNA.
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