Inhibition of CD28-mediated natural cytotoxicity by KIR2DL2 does not require p56(lck) in the NK cell line YT-Indy. |
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| Authors: | Raquel Tarazona Francisco Borrego Maria D Galiani Enrique Aguado Jose Pe?a John E Coligan Rafael Solana |
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| Affiliation: | Faculty of Medicine, Department of Immunology, Reina Sofía Hospital, University of Córdoba, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain. |
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| Abstract: | CD28 functions as a cytotoxicity activation receptor in the NK cell line YT-Indy. To analyze the requirement of p56(lck) kinase in the function of killer inhibitory receptors, we transfected the p56(lck) negative YT-Indy cell line with the cl43 gene encoding for KIR2DL2. Pervanadate treatment revealed KIR2DL2 phosphorylation in YT-Indy-cl43, as well as SHP1/SHP2 recruitment. YT-Indy-cl43 cells were inhibited in their ability to lyse target cells expressing HLA-Cw3, a ligand for KIR2DL2. This inhibition was blocked by anti-KIR2DL2 or anti-HLA class I mAb. CD28 crosslinking on YT-Indy-cl43 enhanced tyrosine phosphorylation of PLC-gamma1. The simultaneous ligation of KIR2DL2 with mAb resulted in a decrease in CD28-induced tyrosine phosphorylation of PLC-gamma1 confirming that dephosphorylation of this protein is involved in the KIR2DL2-induced inhibition of CD28-mediated cytotoxicity. As YT-Indy-cl43 did not express detectable levels of p56(lck), these results indicate that this kinase is not required for transmitting the negative signals generated by KIR2DL2 ligation. |
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