title: Isolation and characterization of a T-lymphocyte somatic mutant with altered signal transduction by the antigen receptor.
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.
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143.
authors.forename: M A
authors.initials: MA
authors.lastname: Goldsmith
authors.forename: A
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D007295:Inositol Phosphates; D011948:Receptors, Antigen, T-Cell; D002118:Calcium