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The Journal of Immunology, 2001, 167: 6773-6779.
Copyright © 2001 by The American Association of Immunologists

Essential Contribution of Germline-Encoded Lysine Residues in J{gamma}1.2 Segment to the Recognition of Nonpeptide Antigens by Human {gamma}{delta} T Cells1

Fumi Miyagawa*,{ddagger}, Yoshimasa Tanaka{dagger}, Seiji Yamashita{dagger}, Bunzo Mikami§, Kiichiro Danno{ddagger}, Masami Uehara{ddagger} and Nagahiro Minato2,*,{dagger}

* Department of Immunology and Cell Biology, Graduate School of Medicine, and {dagger} Graduate School of Biostudies, Kyoto University, Kyoto, Japan; {ddagger} Department of Dermatology, Shiga University of Medical Science, Ohtsu, Shiga, Japan; and § Department of New Food Design, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto, Japan

Human {gamma}{delta} T cells display unique repertoires of Ag specificities largely imposed by selective usages of distinct V{gamma} and V{delta} genes. Among them, V{gamma}2/V{delta}2+ T cells predominate in the circulation of healthy adults and respond to various microbial small molecular mass nonpeptide Ags. The present results indicate that the primary V{gamma}2/V{delta}2+ T cells stimulated with the distinct groups of nonpeptide Ags, including monoethyl pyrophosphate, isobutyl amine, and aminobisphosphonate, invariably exhibit J{gamma}1.2 in the V{gamma}2+ TCR-{gamma} chains. Gene transfer studies revealed that most of the randomly cloned V{gamma}2/J{gamma}1.2+ TCR-{gamma} genes bearing diverse V{gamma}/J{gamma} junctional sequences could confer the responsiveness to all these nonpeptide Ags, while none of the V{gamma}2/J{gamma}1.1+ or V{gamma}2/J{gamma}1.3+ TCR-{gamma} genes could do so. Furthermore, mutation of the lysine residues encoded by the J{gamma}1.2 gene, which are unique in human J{gamma}1.2 and absent in other human or mouse J{gamma} segments, completely abrogated the responsiveness to all the nonpeptide Ags without affecting the response to anti-CD3 mAb. These results strongly suggested that the positively charged lysine residues in the TCR-{gamma} chain CDR3 region encoded by the germline J{gamma}1.2 gene play a key role in the recognition of diverse small molecular mass nonpeptide Ags.




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