IMMUNE CELL INTERACTIONS IN THE RESPONSE TO EB VIRUS

Project: Research project

Project Details

Description

The major objective is to isolate and characterize in vitro human helper T
cell clones (TH) which recognize autologous Epstein-Barr virus-transformed
B lymphoblastoid cell lines (aEBV-BCL). These TH will recognize
EBV-induced cell surface antigens in conjunction with human Ia molecules on
the BCL. Thus, an in vitro system will be developed which will allow the
study of the initiation of specific immune responses to EBV at the cellular
and immunogenetic level. Further, the two cell lines involved (TH and
EBV-BCL) will be homogeneous and provide a readily available source of
material for the biochemical and molecular genetic study of the molecules
involved in this specific cellular interaction. The specific aims of the
project are (1) to define LYDMA, that is EBV-induced antigen(s) involved in
TH responses (2) to investigate the mechanisms of antigen presentation and
Ia restriction involving EBV-induced antigens (3) to determine how T cells
and/or T cell factors regulate EBV infection and transformation of B cells
in vitro (4) to probe the cell surface molecules involved in aims 1-3 via
monoclonal antibodies. Immune response involving EBV are highly relevant to a number of clinical
syndromes. These include 1) Infectious mononucleosis (IM), 2) Burkitt's
lymphoma (BL), 3) X-linked lymphoproliferative disease (XLP), 4) Rheumatoid
arthritis (RA) and, possibly, 5) Acquired immune deficiency syndrome
(AIDS). Each of these syndromes involves significant clinical and/or
laboratory anomalies of the immune system in which TH specific for EBV
almost certainly participate. After information is obtained on
EBV-specific TH from normal subjects, attention will be turned to
investigating TH responses in these specific disease states. The methods
involved in this project are primarily applications of recently developed
techniques. T cell cloning and monoclonal antibody production will produce
the necessary cellular and biological reagents. The system will then be
analyzed by cell proliferation assays, RIA and ELISA, immunoprecipitation
and "Western" blotting, and fluorescence flow cytometry (FACS). EBV-BCL
and EBV-specific TH cell clones will be co-cultured to measure T cell
proliferation and B cell antibody secretion. The effects of mcAbs made
against the two cell lines will be tested by adding to co-cultures.
Antibodies that alter T or B cell function will be used to study
biochemically the cell surface molecule(s) involved.
StatusFinished
Effective start/end date12/1/8411/30/87

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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