1. ¹Laboratoire Cytokines et Immunologie des tumeurs Humaines, INSERM U487, Institut Gustave Roussy, F-94805 Villejuif, Cedex, France
2. ²Dipartimento di Medicina Sperimentale, Sezione di Istologia, and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, 16132 Genova, Italy
3. ³INSERM U448, Faculté de Médecine de Créteil, 94010 Créteil, Cedex, France

Correspondence: F Mami-Chouaib, U487 INSERM, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France. E-mail: cfathia@igr.fr

Abstract

T lymphocytes infiltrating a human lung carcinoma stimulated in vitro with autologous tumor cell line showed a TCRV13.6⁺ T-cell expansion. This subset was isolated using TCRV-specific antibody and several T-cell clones were generated. All these clones expressed a unique V13.6-J2.7 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 IFN 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.