Absence of High-Affinity Binding Sites for Interferon α/β in Variant Murine CD4⁺ T Lymphocytes Not Expressing the T Cell Antigen Receptor

The T cell antigen receptor complex (CD3/Ti) plays a role in specific antigen recognition as well as in signal transduction, with its surface expression required for the function of several other structurally distinct receptor systems, including CD2, Ly-6(TAP), and Thy-1. In this communication, evidence is presented suggesting an association between 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 proliferative responses and their capacity to be inhibited by type 1 IFN with the wild-type, CD3/Ti-positive T cell clone and its CD3/Ti-negative variants. The CD3/Ti-negative variants did not respond to specific antigen or anti-CD3 antibody stimulation but they did respond to T cell growth factor (TCGF), stimulation as did the wild-type parental cells. Therefore, the type 1 IFN inhibition of TCGF-stimulated proliferative responses of wild-type and variant cells were compared. Both natural and recombinant type 1 IFNs inhibited TCGF-induced tritiated thymidine (3H-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-β was 10,000 U/ml, but this same dose of human IFN-αA/D gave only a marginal inhibitory effect. Accompanying the loss of IFN responsiveness, these variants also exhibited a loss of high-affinity type 1 IFN receptors. Taken together, these data suggest that the CD3/Ti complex plays a role in the surface expression of the type 1 IFN receptor in a CD4+ T cell clone. Given the role of the CD3/Ti in several other receptor systems, the present observations further implicate the central position of the CD3/Ti complex in orchestrating ligand-receptor events on the T cell surface. © 1995, Mary Ann Liebert, Inc. All rights reserved.