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

Oncogene volume 22, pages 7192–7198 (2003)Cite this article

Abstract

T lymphocytes infiltrating a human lung carcinoma stimulated in vitro with autologous tumor cell line showed a TCRVβ13.6+ T-cell expansion. This subset was isolated using TCRVβ-specific antibody and several T-cell clones were generated. All these clones expressed a unique Vβ13.6-Jβ2.7 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 IFNγ 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.

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Acknowledgements

We thank S Megherat, Y Lecluse for FACS analyses, R Tamouza and D Charron for HLA typing and D Grunenwald from the Thoracic Surgery Department of Institut Mutualiste Montsouris, Paris, France. This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut Gustave Roussy, the Association pour la Recherche sur le Cancer (Grants 9307, 5253, 2129), the Fondation de France and GEFLUC and the associazione Italiana per la Ricerca sul cancro (AIRC). HE was supported by a fellowship from the Fondation de France (Comité tumeurs solides).

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Authors and Affiliations

  1. Laboratoire Cytokines et Immunologie des tumeurs Humaines, INSERM U487, Institut Gustave Roussy, Villejuif, F-94805, Cedex, France

    Guillaume Dorothée, Hamid Echchakir, Béatrice Le Maux Chansac, Isabelle Vergnon, Faten El Hage, Salem Chouaib & Fathia Mami-Chouaib

  2. Dipartimento di Medicina Sperimentale, Sezione di Istologia, and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Genova, 16132, Italy

    Alessandro Moretta

  3. INSERM U448, Faculté de Médecine de Créteil, 94010 Créteil, Cedex, France

    Armand Bensussan

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  1. Guillaume Dorothée
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Correspondence to Fathia Mami-Chouaib.

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Dorothée, G., Echchakir, H., Chansac, B. et al. Functional and molecular characterization of a KIR3DL2/p140 expressing tumor-specific cytotoxic T lymphocyte clone infiltrating a human lung carcinoma. Oncogene 22, 7192–7198 (2003). https://doi.org/10.1038/sj.onc.1206627

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