ANALYSIS OF EPSTEIN BARR/VIRUS C3D RECEPTORS IN T LYMPHOCYTES

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The Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis and is associated with certain human neoplasias. EBV targets its host cells by binding to a specific surface glycoprotein of 145 kD in size. This receptor also interacts with the third component of the complement cascade, C3 and thus it has been termed complement receptor type 2, abbreviated CR2. Increasing evidence implicated EBV in cancers of T lymphocytes, particularly in association with other viral infections such as HIV. The recent work from our laboratory is of particular interest to the association of EBV with T lymphomas. We have demonstrated that receptors for EBV are expressed on cells of the T lineage, particularly immature thymocytes. Furthermore, thymocytes can be infected upon exposure to the virus and the virus, along with Interleukin 2, can cause the proliferation of thymocytes in a synergistic fashion. In order to study the biological properties of CR2 on thymocytes, we have generated thymocyte clones by infection with HTLV-1. One of the isolated clones, termed TC91+, expresses relatively high amounts of CR2 ad it requires Interleukin 2 for its growth. The TC91+ cells will be thoroughly characterized phenotypically by immunofluorescence and immunoprecipitation utilizing monoclonal antibodies to various lymphocyte differentiation and activation markers. The gene coding for CR2 in TC91+ cells will be clones, sequenced and compared to the known gene. The ability of EBV to infect TC91+ cells and the effects of HTLV-1 upon this infection will be studied. Finally, the biologic effects of CR2 perturbation will be tested by exposing TC91+ to CR2 ligand such as C3, EBV, EBV-gp350, and anti-CR2 monoclonal antibodies. The main source of funding for the work proposed above is being furnished by NIH grant GM39518 which provides support from 12/1/92 to 11/30/95 with plans to be competitively renewed at that time. The importance of EBV in human disease and the relevance of the proposed work to biomedicine is expected to attract and motivate qualified minority students to be involved in the research. The students involved in the studies proposed above will be working under the direct supervision of the principal investigator and will be interacting at both the technical and academic levels with other members of the laboratory. The previous track record of the investigator in successfully training minority students, his vigorous and active research program, and good level of funding guarantee an environment conducive to learning and research training.