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International Immunology, Vol. 15, No. 11, pp. 1301-1307, November 2003
© 2003 Japanese Society for Immunology

Recognition mechanism of non-peptide antigens by human {gamma}{delta} T cells

Seiji Yamashita1, Yoshimasa Tanaka1,4, Masashi Harazaki2, Bunzo Mikami3 and Nagahiro Minato1

1 Department of Immunology and Cell Biology, Graduate School of Biostudies and 2 Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan 3 Laboratory of Food Quality Design and Development, Graduate School of Agriculture, Kyoto University, Kyoto 611-0011, Japan 4 PRESTO, JST, Kyoto, Japan

Correspondence to: N. Minato; E-mail: minato{at}imm.med.kyoto-u.ac.jp
Transmitting editor: S. Koyasu

The majority of {gamma}{delta} T cells in adult human blood exhibit V{gamma}2/V{delta}2-TCR and specifically respond to various kinds of non-peptide antigens. In this study, we comparatively analyzed the CDR3 repertoires of V{gamma}2-{gamma} and V{delta}2-{delta} chain genes in the adult and cord blood. It was confirmed that the vast majority of adult {gamma}{delta} T cells exhibited V{gamma}2-{gamma} chains bearing a J{gamma}1.2 segment with no or short N-region and V{delta}2-{delta} chains with a conserved hydrophobic residue (leucine, valine or isoleucine) at position 97 encoded by N-region of V{delta}/J{delta} junction ({delta}L97). The cord blood cells stimulated with pyrophosphomonoester antigen in vitro showed preferential expansion of the {gamma}{delta} T cells expressing V{gamma}2- and V{delta}2-TCR chains with these structural features as compared with those stimulated with a polyclonal mitogen phytohemagglutinin. TCR gene transfer studies indicated that alanine substitution of lysine at position 108 in J{gamma}1.2 ({gamma}K108) or {delta}L97 abrogated the responsiveness of V{gamma}2/V{delta}2-TCR to all kinds of the non-peptide antigens without affecting the response to anti-CD3 antibody. Furthermore, alanine substitution of arginine at position 51 in V{delta}2 segment ({delta}R51) adjacent to {gamma}K108 in the V{gamma}2/V{delta}2-{gamma}{delta} TCR also abolished the antigen responsiveness. These results strongly suggested that a hydrophobic and two cationic residues ({delta}L97, {gamma}K108 and {delta}R51) clustered in a particular topology at the surface edge of the pocket structure of V{gamma}2/V{delta}2-{gamma}{delta} TCR played essential roles in the recognition of non-peptide antigens.

Keywords: {gamma}{delta} TCR, antigen recognition, antigenic selection, infection immunity, pyrophosphomonoester antigen


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