Paula Kavathas, PhD

Gene Regulation: We created transgenic animals with pieces of human DNA from the human CD8 gene complex (alpha and beta genes) and were able to obtain correct developmental expression of the genes. To localize regulatory elements, we performed sequence analysis, DNase I hypersensitivity mapping, and MAR (matrix attachment region) analysis. We identified several striking regions and are performing further transgenic and knockout studies to firmly establish the presence of regulatory elements. Structure/Funtion Analysis: The CD8 protein interacts with ligands on the outside of the cell (i.e. MHC class I) and with molecules on the inside of the T cell (i.e. tyrosine kinase p56lck, LAT). It also functions as a coreceptor with the T cell receptor forming a complex with MHC class I. Our goal is to understand in molecular terms how the different protein interactions occur and if there are differences between homo (a/a) vs. heterodimeric (a/b) forms of CD8. Taking advantage of crystallographic information, we perform mutational analysis and create models of how the proteins interact. Immune Response to Chlamydia Trachomatis (Ct): Ct is the most common cause of bacterial sexually transmitted disease (STD) worldwide and of ocular trachoma in developing countries. We are characterizing T cell responses to the major outer membrane protein (MOMP) of Ct, a good vaccine candidate. Using special reagents called tetramers, we were able to detect MOMP-specific T cells in the peripheral blood of infected individuals at frequencies that are significant (0.01-0.20% of CD8+ T cells). We plan to continue to characterize these cells with regard to homing receptors and function and will determine their role in immunity to Ct.