Structural basis for immune evasion mechanism of HIV peptide mutations.

在自然杀伤细胞和细胞毒性T细胞上表达的MHC识别受体KIRs和LILRs在病毒感染的调控中起着关键作用。MHC分子上hiv衍生肽的突变破坏T细胞功能，并通过增加抑制性KIR的结合活性来抑制NK功能。在这里，我们成功地在低分辨率下确定了LILR- mhc复合物的结构，揭示了该复合物的结构与先前报道的LILR- mhc复合物相似，LILR识别远离肽结合区域的位点，因此HIV肽突变不太可能影响LILR的结合，这得到了我们的结合研究的支持。另一方面，我们还测定了显示HIV突变肽增加KIR结合的MHC I类分子的晶体结构，揭示了KIR结合活性变化的分子机制。

MHC recognizing receptors expressed on natural killer cells and cytotoxic T cells, KIRs and LILRs, have a pivotal role on regulation of virus infection. The mutation of a HIV-derived peptide on MHC molecule disrupt T cell function and also inhibit NK function by increasing the binding activity of an inhibitory KIR. Here we successfully determined the structure of a LILR-MHC complex at low resolution, revealing that this complex structure is similar to the previously reported LILR-MHC complexes, LILR recognize the site far from the peptide-binding region and thus the HIV peptide mutations do not likely affect the LILR binding, supported by our binding study. On the other hand, we also determined the crystal structure of the MHC class I molecule displaying the HIV mutant peptide, which increased the KIR binding, revealing the molecular mechanism for the change of KIR binding activity.