Vély F, Olcese L, Bléry M, Vivier E
Centre d'Immunologie INSERM/CNRS de Marseille-Luminy, France.
Immunol Lett. 1996 Dec;54(2-3):145-50. doi: 10.1016/s0165-2478(96)02664-8.
NK- and T-cells express at their surface, members of a multigenic family of killer-cell inhibitory receptors (KIR) for MHC Class I molecules. KIR engagement leads to the inhibition of NK- and T-cell activation programs. These receptors recruit the protein tyrosine phosphatases (PTPase), SHP-1 and SHP-2, upon tyrosine phosphorylation of immunoreceptor tyrosine-based inhibition motif (ITIM) expressed in both human and mouse KIR. We further define the ITIM amino acids sequence required in that recognition and demonstrate the critical role of the phosphoY-2 amino acid residue in this V/IxYxxL/V motif. In addition, using RBL-2H3 cells expressing endogenous Fc epsilonRI receptors as well as transfected CD25/CD3zeta chimera and p58.183 human KIR, we show that KIR inhibitory function requires co-engagement of KIR and ITAM-containing receptors. These results document the pathway used by KIR to down-regulate NK- and T-cell activation programs.
自然杀伤细胞（NK细胞）和T细胞在其表面表达主要组织相容性复合体I类分子（MHC I）的杀伤细胞抑制受体（KIR）多基因家族的成员。KIR的结合会导致NK细胞和T细胞激活程序受到抑制。在人和小鼠KIR中表达的基于免疫受体酪氨酸的抑制基序（ITIM）发生酪氨酸磷酸化后，这些受体招募蛋白酪氨酸磷酸酶（PTPase）——SHP-1和SHP-2。我们进一步确定了该识别过程中所需的ITIM氨基酸序列，并证明了该V/IxYxxL/V基序中磷酸化酪氨酸（pY）-2氨基酸残基的关键作用。此外，利用表达内源性FcεRI受体以及转染的CD25/CD3ζ嵌合体和p58.183人KIR的RBL-2H3细胞，我们发现KIR抑制功能需要KIR与含免疫受体酪氨酸激活基序（ITAM）的受体共同结合。这些结果证明了KIR下调NK细胞和T细胞激活程序所采用的途径。
