Recognition mechanism of non-peptide antigens by human gammadelta T cells

Int Immunol. 2003 Nov;15(11):1301-7. doi: 10.1093/intimm/dxg129.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antigens / immunology*
  • Antigens / metabolism
  • Cations / metabolism
  • Complementarity Determining Regions / immunology
  • DNA, Complementary / genetics
  • DNA, Complementary / immunology
  • Female
  • Fetal Blood / immunology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Sequence Data
  • Peptides / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocytes / immunology*


  • Antigens
  • Cations
  • Complementarity Determining Regions
  • DNA, Complementary
  • Peptides
  • Receptors, Antigen, T-Cell, gamma-delta