期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：26
页码：12601-12603
DOI：10.1073/pnas.1907937116
出版社：The National Academy of Sciences of the United States of America
摘要：Killer cell Ig-like receptors (KIR) are expressed on natural killer (NK) cells, lymphocytes of innate immunity and reproduction. The principal KIR ligands are the polymorphic HLA-A, HLA-B, and HLA-C glycoproteins of the human major histocompatibility complex. The KIR form 4 phylogenetic lineages. Lineage III KIR are most numerous and include all KIR that recognize epitopes of HLA-C, the most important KIR ligands. Well established is the role of inhibitory lineage III KIR in educating NK cells to be tolerant of healthy cells and ready to kill infected or malignant cells. By comparison, functions for the activating lineage III KIR have proved elusive, particularly for KIR2DS4, the most common activating KIR. As reported in PNAS (1), Sim et al. find KIR2DS4 has a binding site with much narrower specificity for HLA-C and peptide than the inhibitory KIR. In prokaryote genomes, they identify a highly conserved nonamer sequence in bacterial recombinase A. The corresponding peptide binds HLA-C*05:01, forming a ligand that activates human NK cells bearing KIR2DS4. The potential of this ligand−receptor combination is to make NK cell responses against many different bacterial infections. That the KIR2DS4 ligand is now clearly seen to be a combination of HLA-C*05:01 and a common bacterial peptide is a discovery that should encourage and invigorate future research on other orphan KIR. NK cells were first studied in the context of killing tumor cells that escaped CD8 T cell attack by reducing their surface expression of MHC class I (2). During development, human NK cells acquire activating and inhibitory receptors that recognize variable HLA-A, HLA-B, and HLA-C, and conserved HLA-E. Inhibitory HLA class I receptors educate developing NK cells (3), creating a dynamic intracellular balance between activating and inhibitory signals. This balance ensures that NK cells do not disturb healthy cells but promptly respond to the lower.
