Winter C C, Gumperz J E, Parham P, Long E O, Wagtmann N
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852-1727, USA.
J Immunol. 1998 Jul 15;161(2):571-7.
Cytotoxicity of human NK cells is under negative control of killer cell Ig-like receptors (KIR) specific for HLA class I. To determine the specificity of five KIR containing two Ig domains (KIR2D), direct binding of soluble recombinant KIR2D to a panel of HLA class I transfectants was assayed. One soluble KIR2D, derived from an inhibitory receptor with a long cytoplasmic tail (KIR2DL1), bound to HLA-C allotypes containing asparagine 77 and lysine 80 in the heavy chain, as expected, since these allotypes inhibit lysis by NK cells expressing KIR2DL1. Surprisingly, another KIR2D (KIR2DL2), which inhibits NK lysis of cells expressing HLA-C molecules with serine 77 and asparagine 80, bound to HLA-C allotypes carrying either amino acid motif. Expression of the KIR2DL receptors in NK cells using recombinant vaccinia viruses confirmed these patterns of recognition, and identified KIR2DL3 as another KIR reacting with both groups of HLA-C allotypes. Mutagenesis of amino acid 44 in KIR2DL1 and KIR2DL2 suggested this residue controls the affinity of KIR for the 77/80 motif of HLA-C molecules. Two other soluble KIR2D, derived from noninhibitory receptors with short cytoplasmic tails (KIR2DS), did not bind to any of the HLA class I allotypes tested. One of these receptors (KIR2DS2) is closely related in sequence to KIR2DL2. Substitution of tyrosine 45 with the phenylalanine conserved in other KIR was sufficient to permit specific binding of KIR2DS2 to HLA-C. These results show that KIR2DL receptors are specific for HLA-C, but that recognition of HLA-C allotypes appears more permissive than indicated by previous functional experiments.
人类自然杀伤细胞（NK细胞）的细胞毒性受针对I类HLA的杀伤细胞免疫球蛋白样受体（KIR）的负调控。为了确定含两个免疫球蛋白结构域的五种KIR（KIR2D）的特异性，检测了可溶性重组KIR2D与一组I类HLA转染细胞的直接结合情况。一种源自具有长细胞质尾巴的抑制性受体的可溶性KIR2D（KIR2DL1），如预期的那样，与重链中含有天冬酰胺77和赖氨酸80的I类HLA-C同种异型结合，因为这些同种异型抑制表达KIR2DL1的NK细胞的裂解作用。令人惊讶的是，另一种抑制表达丝氨酸77和天冬酰胺80的I类HLA-C分子的细胞的NK裂解作用的KIR2D（KIR2DL2），与携带任何一种氨基酸基序的I类HLA-C同种异型结合。利用重组痘苗病毒在NK细胞中表达KIR2DL受体证实了这些识别模式，并确定KIR2DL3是另一种与两组I类HLA-C同种异型反应的KIR。KIR2DL1和KIR2DL2中氨基酸44的诱变表明该残基控制KIR对I类HLA-C分子77/80基序的亲和力。另外两种源自具有短细胞质尾巴的非抑制性受体的可溶性KIR2D（KIR2DS），未与所检测的任何一种I类HLA同种异型结合。这些受体之一（KIR2DS2）在序列上与KIR2DL2密切相关。将酪氨酸45替换为其他KIR中保守的苯丙氨酸足以使KIR2DS2特异性结合I类HLA-C。这些结果表明，KIR2DL受体对I类HLA-C具有特异性，但I类HLA-C同种异型的识别似乎比先前功能实验所表明的更为宽松。
