MOLECULAR AND FUNCTIONAL STUDIES OF TCA3

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DESCRIPTION (Adapted from Applicant's abstract and Specific Aims.): Over the last eight years, this investigator has isolated a cDNA expressed in antigen or mitogen-stimulated T-cells, identified it as a pro-inflammatory cytokine of the beta-chemokine family, shown that it can be expressed in two forms: TCA3 and P500, and that the two forms differ in chemotactic activity (neutrophil/monocyte and monocytes/macrophages, respectively). The gene was cloned and mapped to mouse chromosome 11. Furthermore, as part of an attempt to study the biological activity of this chemokine, the investigator found that TCA3-transfected tumor cells failed to grow in syngeneic hosts. Animals transplanted with these tumors achieved specific immunity to the tumor cells (even without transfection of TCA3). The questions that will be asked in the present application are: 1. How do the structural differences in TCA3 and P500 correspond to the differences in the specificity of their chemotactic activity? TCA3 and P500 are alternate splice products of the same gene and differ extensively after amino-acid 44 (TCA3 is 69 aa's; P500 is 61aa's long). 2. What cell-types have receptors for these chemokines, and what is the biochemical structure of those receptors? 3. What is the mechanism for the inhibition of tumor growth when tumor cells produce TCA3, and what is the basis of the tumor immunity that develops?