MOUSE AUTOREACTIVE GAMMA/DELTA-T-CELLS .2. 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 V(gamma)1.1C(gamma)4/V(delta)6 type T cell receptor (TcR), but several of the DETC lines also express a second TcR. Sequence analyses of these gamma/delta TcR revealed that the gamma-chains were identical and that the delta-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 V(gamma)1.1C(gamma)4/V(delta)6 receptor and one hybrid a V(gamma)1.1C(gamma)4/V(delta)4 receptor that had a close structural relationship to the DETC-gamma/delta TcR associated with spontaneous lymphokine secretion. Gamma/delta TcR of the C(gamma)4 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, V(gamma)2C(gamma)1 or V(gamma)3C(gamma)1, apparently in association with the same delta-chain that paired with the C(gamma)4 chain. The presence of spontaneous lymphokine-secreting gamma/delta 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.