Killer cell immunoglobulin receptors and T cell receptors bind peptide-major histocompatibility complex class I with distinct thermodynamic and kinetic properties
Killer cell immunoglobulin receptors and T cell receptors bind peptide-major histocompatibility complex class I with distinct thermodynamic and kinetic properties
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DOI：
10.1074/jbc.274.40.28329
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发表时间：
1999-10-01
影响因子：
4.8
通讯作者：
van der Merwe, PA
中科院分区：
文献类型：
--
作者：
Maenaka, K;Juji, T;van der Merwe, PA
人类自然杀伤细胞和T细胞亚群表达一系列杀伤细胞免疫球蛋白受体（KIR），可识别主要组织相容性复合体（MHC）I类分子。KIR和T细胞受体（TCR）以肽依赖性方式与肽-MHC I类复合物的重叠区域结合。具有两个免疫球蛋白结构域的KIR（KIR 2D）识别HLA-C等位基因的不同子集。在这里，我们使用表面等离子体共振来研究KIR 2DL 1和KIR 2DL 3的可溶性形式的结合到几个肽-HLA-Cw 7复合物。KIR 2DL 3以1：1的化学计量和在其它细胞-细胞识别分子（包括TCR）测量的值范围内的亲和力（K-d在25 ℃下类似于7 μ M）结合呈递肽RYRPGTVAL的HLA-Cw 7等位基因。尽管据报道KIR 2DL 1在功能测定中不识别HLA-Cw 7等位基因，但它结合RYRPGTVAL/HLA-Cw 7，尽管亲和力低10-20倍。TCR/肽-MHC相互作用的特征在于相对缓慢的动力学和不利的熵变化（威尔考克斯，B. E、Gao，G. F.、呃，J. R.，Ladbury，J.E.，贝尔，J. I.，雅各布森，B。K，和货车der Merwe，P. A.（1999）Immunity 10，357-365），表明结合伴随着构象调整。相反，我们发现KIR 2DL 3以快速动力学和有利的结合熵结合RYRPGTVAL/HLA-Cw 7，与刚体缔合一致。这些结果表明，KIR/肽-MHC I类相互作用具有其他细胞-细胞识别分子的典型性质，并且它们突出了TCR/肽-MHC识别的不寻常性质。
Human natural killer cells and a subset of T cells express a repertoire of killer cell immunoglobulin receptors (KIRs) that recognize major histocompatibility complex (MHC) class I molecules. KIRs and T cell receptors (TCRs) bind in a peptide-dependent manner to overlapping regions of peptide-MHC class I complexes. KIRs with two immunoglobulin domains (KIR2Ds) recognize distinct subsets of HLA-C alleles. Here we use surface plasmon resonance to study the binding of soluble forms of KIR2DL1 and KIR2DL3 to several peptide-HLA-Cw7 complexes. KIR2DL3 bound to the HLA-Cw7 allele presenting the peptide RYRPGTVAL with a 1:1 stoichiometry and an affinity (K-d similar to 7 mu M at 25 degrees C) within the range of values measured for other cell-cell recognition molecules, including the TCR. Although KIR2DL1 is reported not to recognize the HLA-Cw7 allele in functional assays, it bound RYRPGTVAL/HLA-Cw7, albeit with a 10-20-fold lower affinity. TCR/peptide-MHC interactions are characterized by comparatively slow kinetics and unfavorable entropic changes (Willcox, B. E., Gao, G. F., WS er, J. R., Ladbury, J. E., Bell, J. I., Jakobsen, B. K,, and van der Merwe, P. A. (1999) Immunity 10, 357-365), suggesting that binding is accompanied by conformational adjustments. In contrast, we show that KIR2DL3 binds RYRPGTVAL/HLA-Cw7 with fast kinetics and a favorable binding entropy, consistent with rigid body association. These results indicate that KIR/peptide-MHC class I interactions have properties typical of other cell-cell recognition molecules, and they highlight the unusual nature of TCR/peptide-MHC recognition.