Autoaggressive myocytotoxic T lymphocytes expressing an unusual gamma/delta T cell receptor

doi:10.1084/jem.176.6.1785

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Autoaggressive myocytotoxic T lymphocytes expressing an unusual gamma/delta T cell receptor

G Pluschke, D Ruegg, R Hohlfeld and AG Engel
Department of Molecular Biology, Ciba-Geigy Ltd., Basel, Switzerland.

Polymyositis mediated by gamma/delta T cells is a unique disease in which autoaggressive T lymphocytes surround, invade, and destroy muscle fibers. Histochemically, the vast majority of muscle-infiltrating T cells in a patient with polymyositis were reactive with a pan- gamma/delta T cell receptor (TCR)-specific monoclonal antibody (TCR- delta 1+), but unlike > 90% of peripheral blood gamma/delta T cells, these lymphocytes did not react with V delta 1- or V gamma 9-specific antibodies (A13- and Ti gamma A-, respectively). Differential reactivity with two different V delta 2-specific monoclonal antibodies (BB3-/TiV-delta 2+) indicated that the infiltrating T cells express a V delta 2-containing TCR with unusual additional structural features. Using conventional and anchored polymerase chain reaction for the analysis of TCR transcripts, we found a striking predominance of one unusual V delta 2-J delta 3 recombination and one V gamma 3-J gamma 1 recombination. Both the unusual phenotype (TCR-delta 1+/A13-/Ti gamma A- /BB3-/TiV-delta 2+) and the dominance of distinct TCR transcripts are compatible with the assumption that one T cell clone, which expresses a V gamma 3-J gamma 1-C gamma 2/V delta 2-J delta 3-C delta disulfide- linked TCR, dominates among the infiltrating T cells of the polymyositis muscle specimen analyzed.
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