Functional and molecular characterization of a KIR3DL2/p140 expressing tumor-specific cytotoxic T lymphocyte clone infiltrating a human lung carcinoma

Oncogene. 2003 Oct 16;22(46):7192-8. doi: 10.1038/sj.onc.1206627.


T lymphocytes infiltrating a human lung carcinoma stimulated in vitro with autologous tumor cell line showed a TCRVbeta13.6(+) T-cell expansion. This subset was isolated using TCRVbeta-specific antibody and several T-cell clones were generated. All these clones expressed a unique Vbeta13.6-Jbeta2.7 TCR with the same junctional region strongly suggesting that they derived from the same cell. They were CD8(+)/CD28(-) and expressed the MHC class I binding killer cell Ig-like receptor (KIR)3DL2/p140, but not KIR3DL1/p70, KIR2DL1/p58.1 and KIR2DL2/3/p58.2. Sequence analysis indicated that KIR3DL2/p140 cDNA was identical to the previously reported 3DL2*002 allele except for two nucleic acid substitutions. Functional studies showed that KIR3DL2/p140(+) CTL secrete a significant level of IFNgamma and mediate an HLA-A2-restricted cytotoxicity against the autologous and some allogeneic tumor cells but not towards the autologous EBV-B cells. Strikingly, both the lytic and the cytokine secretion activities induced upon specific cell interactions were unaffected by anti-KIR3DL2/p140 antibody. In addition, crosslinking KIR3DL2/p140 molecules on CTL did not result into the modification of cytotoxicity and cytokine production triggered by anti-CD3 antibody. These results strongly suggest that, as opposed to distinct KIR expressed by CTL, the in vitro KIR3DL2/p140 engagement does not result into inhibitory (nor activatory) effects on tumor-specific CTL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clone Cells
  • Cytotoxicity, Immunologic
  • Fluorescent Antibody Technique
  • Humans
  • Killer Cells, Natural / immunology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, KIR
  • Receptors, KIR2DL1
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3
  • Receptors, KIR3DL1
  • Receptors, KIR3DL2
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • T-Lymphocytes, Cytotoxic / physiology*
  • Tumor Cells, Cultured


  • Antigens, CD
  • KIR2DL2 protein, human
  • KIR2DL3 protein, human
  • KIR3DL1 protein, human
  • KIR3DL2 protein, human
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL1
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3
  • Receptors, KIR3DL1
  • Receptors, KIR3DL2