The Epstein-Barr Virus (EBV) is the causative agent of infectious mononucleosis, and is associated with certain human neoplasias. EBV is thought to display exclusive tropism for B lymphocytes and epithelial cells. The virus targets these cells via specific surface receptors which are also reactive with enzymatic fragments of the third component of complement (EBV/C3d receptors). Recent reports have described the cases of patients with EBV-genome positive T cell lymphomas thus, suggesting that EBV could be involved in cancers of T cells not previously appreciated. Previous studies from our laboratory have demonstrated the presence of EBV/C3d receptors on cells of the T lineage thus, challenging the exclusive B lymphocyte, epithelial cell tropism of this virus. In particular, we have shown that immature human thymocytes, in contrast to mature peripheral T cells, express EBV/C3d receptors. The binding of EBV to the thymocyte receptors displays specificity, evidenced by the ability of monoclonal anti-EBV/C3d receptor antibodies and C3 to inhibit viral binding, and results in the infection of the cells. Phenotypic analysis with monoclonal antibodies that are reactive with distinct epitopes of the B cell EBV/C3d receptors has revealed differential reactivity of T cells with these reagents. This phenomenon stands in contrast to the equivalent reactivity of B cells. One interpretation of the different reactivities could be that the EBV/C3d receptors on T cells might be structurally different from those on B lymphocytes. This interpretation in turn, suggests that there might be more than one gene coding for EBV/C3d receptors. Thus, the overall objective of this research is a more detailed structural and functional characterization of the T cell EBV/C3d receptors and their comparison to those on B lymphocytes. The specific objectives are (1) Characterization of the thymocyte subpopulation which expresses EBV/C3d receptors by using a battery of differentiation specific and anti-T cell monoclonal antibodies. (3) Similar phenotypic analysis of a panel of T-cell leukemic lines which represent various stages of T lymphocyte differentiation. (3) Testing the binding of C3 and its enzymatic fragments to thymocytes and T cell lines and comparing it to the binding on B cells. (4) Assessment of the functional consequences of C3 fragments, synthetic C3 peptides, monoclonal anti-EBV/C3d receptor antibodies, and EBV interaction with thymocytes and T cell lines. The student involved in these studies will be working under the direct supervision of the principal investigator and will be interacting at both the technical and academic levels with all the other members of the laboratory.
