Thy-1- and Ly-6-mediated lymphokine production and growth inhibition of a T cell hybridoma require co-expression of the T cell antigen receptor complex |
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Authors: | J J Sussman T Saito E M Shevach R N Germain J D Ashwell |
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Institution: | Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892. |
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Abstract: | Repetitive subcloning of an Ag-specific T cell hybridoma yielded a variant that lacked functional mRNA for the Ag receptor (Ti, T cell Ag receptor alpha/beta heterodimer) beta-chains and failed to express CD3/Ti on the cell surface. Transfection with the original Ti alpha- and beta-chain genes restored CD3/Ti expression to normal levels. Whereas the parental T cell hybridoma produced IL-2 when stimulated with mAb against CD3, Thy-1, and Ly-6, the CD3/Ti negative cell failed to do so. Reconstitution of CD3/Ti expression restored normal IL-2 production in response to these mAb. A separate response to activation, the inhibition of transformed growth, was also dependent upon co-expression of CD3/Ti. These data demonstrate that cell surface expression of CD3/Ti is required for IL-2 production and growth inhibition initiated by two distinct activating molecules, and suggest that CD3/Ti may be a final common pathway for many transmembrane activation signals. |
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