Mouse autoreactive γ/δ T cells II. Molecular characterization of the T cell receptor

A panel of dendritic epidermal T cell (DETC) lines, and hybridomas derived from them, has been shown to spontaneously secrete lymphokines in the absence of added stimuli, which suggests that these cells are autoreactive. These cell lines are characterized by the expression of a Vγ1.1Cγ4/Vδ6 type T cell receptor (TcR), but several of the DETC lines also express a second TcR. Sequence analyses of these γ/δ TcR revealed that the γ chains were identical and that the δ chains, while not identical, were quite restricted in diversity, indicating that these receptors may recognize a common or closely related group of antigens. Analysis of hybridomas derived from newborn thymocytes identified six hybridomas that spontaneously secrete lymphokines. Five hybrids expressed a Vγ1.1Cγ4/Vδ6 receptor and one hybrid a Vγ1.1Cγ4/Vδ4 receptor that had a close structural relationship to the DETC γ/δ TcR associated with spontaneous lymphokine secretion. γ/δ TcR of the Cγ4 type expressed by splenic hybridomas that did not spontaneously secrete lymphokines revealed no such relationship. Curiously, like the DETC, several of the thymocyte hybridomas that spontaneously secreted lymphokines expressed a second TcR, Vγ2Cγ1 or Vγ3Cγ1, apparently in association with the same δ chain that paired with the Cγ4 chain. The presence of spontaneous lymphokinesecreting γ/δ T cells with such highly homologous TcR in both the thymus and skin suggests a thymic origin for the autoreactive DETC and that these cells recognize a common or closely related group of self-antigens.