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Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
Published on: October 25, 2016
Functional reconstitution of an immunoglobulin antigen receptor in T cells
T E Costa1, R R Franke, M Sanchez
1Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021.
Humoral immune responses are initiated by binding of antigen to the immunoglobulins (Igs) on the plasma membrane of B lymphocytes. On the cell surface, Ig forms a complex with several other proteins, two of which, MB-1 and B29, have been implicated in receptor assembly. We have reconstituted Ig receptor function in T lymphocytes by transfection of cloned receptor components. We found that efficient transport of IgM to the surface of T cells required coexpression of B29. Furthermore, IgM and B29 alone were sufficient to reconstitute antigen-specific signal transduction by Ig in the transfected T cells. Crosslinking of IgM with either antireceptor antibodies or antigen induced a calcium flux, phosphoinositol turnover, and interleukin secretion in T cells. These experiments establish a requirement for B29 in Ig receptor function, and suggest that the signaling apparatus of T and B cells is structurally homologous.
Humoral immune responses are initiated by binding of antigen to the immunoglobulins (Igs) on the plasma membrane of B lymphocytes. On the cell surface, Ig forms a complex with several other proteins, two of which, MB-1 and B29, have been implicated in receptor assembly. We have reconstituted Ig receptor function in T lymphocytes by transfection of cloned receptor components. We found that efficient transport of IgM to the surface of T cells required coexpression of B29. Furthermore, IgM and B29 alone were sufficient to reconstitute antigen-specific signal transduction by Ig in the transfected T cells. Crosslinking of IgM with either antireceptor antibodies or antigen induced a calcium flux, phosphoinositol turnover, and interleukin secretion in T cells. These experiments establish a requirement for B29 in Ig receptor function, and suggest that the signaling apparatus of T and B cells is structurally homologous.
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