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

Abstract

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.

Development of Dendritic Epidermal T Cells with a Skewed Diversity of γδTCRs in Vδ1-Deficient Mice

“…Notably, an amino acid sequence ((I/V/L)GGIRA) at the V␦6-D␦2-J␦1 junctions was very frequently observed in both V␥5 ϩ and V␥5 Ϫ DETC transcripts (10/17 and 11/20, respectively; data not shown). Such a junctional sequence was previously observed in neonatal thymic hybridomas and DETC lines spontaneously secreting cytokines (38). Only a few V␦6 ϩ clones used D␦1, D␦2, and J␦1 genes, which are typically detected in adult thymocytes (1,37).…”

Depletion of a γδ T Cell Subset Can Increase Host Resistance to a Bacterial Infection

“…22). In addition, previous studies of our own and of others involving the mouse V␥1 subset (23)(24)(25)(26)(27), which expresses a junctionally diverse V␥1-J␥4-C␥4 ␥ chain generally together with either V␦6 or V␦4, revealed an apparent autoreactivity. Specifically, V␥1…”

T‐Cell Receptor Variable γ Chain Gene Expression in the Interaction between Rat γδ‐Type T Cells and Heat‐Shock Protein 70‐Like Molecule

“…In our mouse model, TCR Vγ1/Vδ6 dendritic epidermal Tcell (DETC) line and thymic hybridomas were reported to be autoreactive earlier (5,6,12), though their ligand(s) was not elucidated. They are also heterogeneous with respect to diverse CDR3 regions.…”

“…Hybridoma cells (1ϫ10 5 /well) seeded in a 96-microwell-plate were tested for their reactivity with 0.5ϫ10 5 /well RNK 16, FTL43, and C58 target cells or immobilized mAb V65 as indicated. The supernatants of hybridomas co-cultured with target cells for 12-18 hr were transferred and tested for TNF production.…”

“…This implies that only one amino acid was added in #067-restricted T-cell hybridomas, whereas two or three amino acids were added in #067-non restricted ones. In this study, we also suggested the possible presence of dual T-cell γδ receptors (TCR) (5,10,12), since some T-cell hybridomas exhibited dual in-frame transcripts of TCR Vγ 1 and Vγ 2.…”