ABSENCE OF HIGH-AFFINITY BINDING-SITES FOR INTERFERON-ALPHA BETA IN VARIANT MURINE CD4(+) T-LYMPHOCYTES NOT EXPRESSING THE T-CELL ANTIGEN RECEPTOR/

The T cell antigen receptor complex (CD3/Ti) plays a sole in specific antigen recognition as well as in signal transduction, with its surfac e expression required for the function of several other structurally d istinct receptor systems, including CD2, Ly-6(TAP), and Thy-1. In this communication, evidence is presented suggesting an association betwee n the surface expression of CD3/Ti and that of the type 1 interferon ( IFN) receptor in a CD4(+) murine T cell clone, We tested the prolifera tive responses and their capacity to be inhibited by type 1 IFN with t he wild-type, CD3/Ti-positive T cell clone and its CD3/Ti-negative var iants, The CD3/Ti-negative variants did not respond to specific antige n or anti-CD3 antibody stimulation but they did respond to T cell grow th factor (TCGF), stimulation as did the wild-type parental cells, The refore, the type 1 IFN inhibition of TCGF-stimulated proliferative res ponses of wild-type and variant cells were compared, Both natural and recombinant type 1 IFNs inhibited TCGF-induced tritiated thymidine (H- 3-TdR) incorporation in the wild-type T cell clone, with a ID50 of 60- 80 U/ml. By contrast, the variants required much higher doses of type 1 IFN. The ID50 with natural murine IFN-beta was 10,000 U/ml, but this same dose of human IFN-alpha A/D gave only a marginal inhibitory effe ct, Accompanying the loss of IFN responsiveness, these variants also e xhibited a loss of high-affinity type 1 IFN receptors, Taken together, these data suggest that the CD3/Ti complex plays a role in the surfac e expression of the type 1 IFN receptor in a CD4(+) T cell clone, Give n the role of the CD3/Ti in several other receptor systems, the presen t observations further implicate the central position of the CD3/Ti co mplex in orchestrating ligand-receptor events on the T cell surface.