Recognition mechanism of non-peptide antigens by human gammadelta T cells.
The majority of gammadelta T cells in adult human blood exhibit Vgamma2/Vdelta2-TCR and specifically respond to various kinds of non-peptide antigens. In this study, we comparatively analyzed the CDR3 repertoires of Vgamma2-gamma and Vdelta2-delta chain genes in the adult and cord blood. It was confirmed that the vast majority of adult gammadelta T cells exhibited Vgamma2-gamma chains bearing a Jgamma1.2 segment with no or short N-region and Vdelta2-delta chains with a conserved hydrophobic residue (leucine, valine or isoleucine) at position 97 encoded by N-region of Vdelta/Jdelta junction (deltaL97). The cord blood cells stimulated with pyrophosphomonoester antigen in vitro showed preferential expansion of the gammadelta T cells expressing Vgamma2- and Vdelta2-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 Jgamma1.2 (gammaK108) or deltaL97 abrogated the responsiveness of Vgamma2/Vdelta2-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 Vdelta2 segment (deltaR51) adjacent to gammaK108 in the Vgamma2/Vdelta2-gammadelta TCR also abolished the antigen responsiveness. These results strongly suggested that a hydrophobic and two cationic residues (deltaL97, gammaK108 and deltaR51) clustered in a particular topology at the surface edge of the pocket structure of Vgamma2/Vdelta2-gammadelta TCR played essential roles in the recognition of non-peptide antigens.
Yamashita
Seiji
S
Department of Immunology and Cell Biology, Graduate School of Biostudies and Department of Pediatrics, Kyoto University, Kyoto 606-8501, Japan.
Tanaka
Yoshimasa
Y
Harazaki
Masashi
M
Mikami
Bunzo
B
Minato
Nagahiro
N
D000328:Adult; D000595:Amino Acid Sequence; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D002412:Cations; D022801:Complementarity Determining Regions; D018076:DNA, Complementary; D010455:Peptides; D016692:Receptors, Antigen, T-Cell, gamma-delta