德国莱布尼茨实验病毒学研究所Marcus Altfeld团队一项最新工作，发现一类HLA-DP分子能够作为天然细胞毒性受体NKp44的配体。这一研究成果于2019年9月发表在国际学术期刊《自然—免疫学》上。

研究人员研究了两种主要的自然杀伤（NK）细胞受体家族，杀伤细胞免疫球蛋白样受体（KIR）和天然细胞毒性受体（NCR）是否含有与HLA II类结合的受体，并确定了NK细胞受体NKp44与一类HLA-DP分子的直接相互作用，包括HLA-DP401，白种人群中最常见的II类同种异型之一。使用NKp44ζ阳性报告细胞和原代人NKp44阳性NK细胞，研究人员证明NKp44和HLA-DP401之间的相互作用触发功能性NK细胞反应。HLA-DP分子和NKp44之间的这种相互作用暗示HLA II类作为先天免疫反应的组成部分，这非常类似于HLA I类。它还为HLA-DP亚型与几种疾病结果之间描述的关联提供了潜在的机制，这些疾病包括乙型肝炎病毒感染、移植物抗宿主病和炎症性肠病等。

据介绍，自然杀伤（NK）细胞可以使用激活和抑制受体识别病毒感染和应激细胞，其中许多受体与HLA I类相互作用。尽管早期研究也显示了HLA II类对NK细胞活性的功能影响，但从未发现过特异性识别HLA II类分子的NK细胞受体。

附：英文原文

Title: A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44

Author: Annika Niehrs, Wilfredo F. Garcia-Beltran, Paul J. Norman, Gabrielle M. Watson, Angelique Hlzemer, Anas Chapel, Laura Richert, Andreas Pommerening-Rser, Christian Krner, Mikki Ozawa, Glria Martrus, Jamie Rossjohn, Jar-How Lee, Richard Berry, Mary Carrington, Marcus Altfeld

Issue&Volume: Volume 20 Issue 9

Abstract: Natural killer (NK) cells can recognize virus-infected and stressed cells1 using activating and inhibitory receptors, many of which interact with HLA class I. Although early studies also suggested a functional impact of HLA class II on NK cell activity2,3, the NK cell receptors that specifically recognize HLA class II molecules have never been identified. We investigated whether two major families of NK cell receptors, killer-cell immunoglobulin-like receptors (KIRs) and natural cytotoxicity receptors (NCRs), contained receptors that bound to HLA class II, and identified a direct interaction between the NK cell receptor NKp44 and a subset of HLA-DP molecules, including HLA-DP401, one of the most frequent class II allotypes in white populations4. Using NKp44ζ+ reporter cells and primary human NKp44+ NK cells, we demonstrated that interactions between NKp44 and HLA-DP401 trigger functional NK cell responses. This interaction between a subset of HLA-DP molecules and NKp44 implicates HLA class II as a component of the innate immune response, much like HLA class I. It also provides a potential mechanism for the described associations between HLA-DP subtypes and several disease outcomes, including hepatitis B virus infection5,6,7, graft-versus-host disease8 and inflammatory bowel disease9,10.

DOI: 10.1038/s41590-019-0448-4

Source: https://www.nature.com/articles/s41590-019-0448-4