title: Impaired TCR signal transduction, but normal antigen presentation, in a patient with common variable immunodeficiency.
abstract: We describe a 27-year-old white man with common variable immunodeficiency (CVID) who has two healthy histoidentical brothers and one IgA-deficient sister who shares one HLA haplotype with the patient. T cells from the patient with CVID showed an impaired response to recall antigens (tetanus toxoid, E. coli), whereas his IgA-deficient sister and his two healthy histoidentical brothers responded normally. Cross-mixing experiments using isolated monocytes and T cells from the CVID patient and one histoidentical brother revealed that the patient's monocytes were fully functional in processing and presenting antigen to resting T cells of his brother, and provided normal accessory cell function for superantigen-induced activation of his brother's resting T cells. In contrast, the patient's T cells were unable to respond to antigen presented by the brother's monocytes and failed to respond with an increase in intracellular free Ca++ to stimulation with superantigen, which is known to bind to the TCR V beta-chain outside the antigen-binding groove. However, stimulation with a combination of PMA and IM, directly activating protein kinase C and increasing intracellular free Ca++ by bypassing membrane receptors, induced normal Ca++ flux. These data indicate that the patient with CVID has a defect in TCR-mediated signalling at the level of the T cells which is not present in his histoidentical healthy brothers or in his haploidentical IgA-deficient sister.
authors: Institute of Immunology, University of Vienna, Austria.
authors: M B
authors: MB
authors: Fischer
authors: I
authors: I
authors: Hauber
authors: H M
authors: HM
authors: Wolf
authors: E
authors: E
authors: Vogel
authors: J W
authors: JW
authors: Mannhalter
authors: M M
authors: MM
authors: Eibl
mesh_terms: D000293:Adolescent; D000328:Adult; D017951:Antigen Presentation; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D017074:Common Variable Immunodeficiency / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013745:Tetanus Toxoid / Q000276:immunology
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; D013745:Tetanus Toxoid; D002118:Calcium