Functional and molecular characterization of a KIR3DL2/p140 expressing tumor-specific cytotoxic T lymphocyte clone infiltrating a human lung carcinoma.
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.
Dorothée
Guillaume
G
Laboratoire Cytokines et Immunologie des tumeurs Humaines, INSERM U487, Institut Gustave Roussy, F-94805 Villejuif, Cedex, France.
Echchakir
Hamid
H
Le Maux Chansac
Béatrice
B
Vergnon
Isabelle
I
El Hage
Faten
F
Moretta
Alessandro
A
Bensussan
Armand
A
Chouaib
Salem
S
Mami-Chouaib
Fathia
F
D015703:Antigens, CD / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1; D054347:Receptors, KIR3DL2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human; C515083:KIR3DL1 protein, human; C515084:KIR3DL2 protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1; D054347:Receptors, KIR3DL2