Abstract
We have developed an approach for deriving and characterizing antigen-receptor (CD3/Ti) signal-transduction mutants. This strategy combines receptor-mediated growth inhibition and fluorescence-activated cell sorting with the Ca2+-indicator indo-1. Despite the expression of structurally normal CD3/Ti complexes, one such mutant (J.CaM1) fails to exhibit inositolphospholipid metabolism or Ca2+ mobilization in response to anti-CD3 or anti-Ti monoclonal antibodies and fails to produce lymphokines in response to these antibodies. Surprisingly, anti-Ti antibody retains its effectiveness as a stimulus for the down-regulation of CD3/Ti surface expression. These cells remain responsive to AIF-4, at least one anti-CD3 antibody, and some combinations of nonagonist anti-Ti and anti-CD3 antibodies. The mutation in J.CaM1 appears to lie in a proximal component of the signal-transduction apparatus.
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Selected References
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