Gene transfer demonstrates that the Vγ1.1Cγ4Vδ6Cδ T cell receptor is essential for autoreactivity

Gary E. Kikuchi, Kevan Roberts, Ethan M. Shevach, John E. Coligan

Research output: Contribution to journalArticlepeer-review

Abstract

Murine T cell lines and hybridomas derived from the epidermis that express the Vγ1.1Cγ4Vδ6Cδ TCR and may, therefore, recognize an autoantigen, secrete cytokines spontaneously in culture. In addition, activation of these cells requires engagement of the vitronectin receptor (VNR) by extracellular matrix proteins. To further evaluate the role of the TCR, the VNR, and the putative autoantigen in the activation of this T cell subset, we cloned complete cDNA encoding the Vγ1.1Cγ4 and Vδ6Cδ TCR and transfected the cDNA constructs into a TCR- murine hybridoma and into a TCR- variant of the human Jurkat line. The murine transfectant spontaneously produced IL-2 in culture and IL-2 production could be inhibited by anti-CD3, anticlonotypic mAb to the transfected TCR, and anti-VNR mAb, as well as by RGDS. These results demonstrate that transfection of the γδ TCR confers to recipient T cells the phenotype of constitutive activation, as well as dependence on engagement of the VNR as an accessory molecule. In contrast, the Jurkat γδ transfectant failed to produce cytokines spontaneously, although the transfected TCR was capable of signal transduction after stimulation by anti-TCR mAb. Surprisingly, neither the murine transfectant nor the human transfectant could be induced to respond to autoantigen bearing cells in coculture assays. One interpretation of these results is that coexpression on the surface of the same cell of the Vγ1.1 Vδ6 TCR, the VNR, and a putative autoantigen are necessary for T cell activation in this system.

Original languageEnglish
Pages (from-to)1302-1307
Number of pages6
JournalJournal of Immunology
Volume148
Issue number5
StatePublished - Mar 1 1992

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