Ruggeri Loredana, Mancusi Antonella, Burchielli Emanuela, Perruccio Katia, Aversa Franco, Martelli Massimo F, Velardi Andrea
Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Policlinico Monteluce, Via Brunamonti 51, Perugia, Italy.
Semin Cancer Biol. 2006 Oct;16(5):404-11. doi: 10.1016/j.semcancer.2006.07.007. Epub 2006 Jul 8.
Human NK cell function is regulated by clonally distributed inhibitory receptors termed "Killer cell Immunoglobulin-like Receptors" (KIRs) that recognize epitopes ("KIR ligands") shared by HLA-C and HLA-B class I allele groups and every functional NK cell in the repertoire expresses at least one receptor for self HLA-class I molecules. Consequently, when NK cells are confronted with allogeneic targets which do not express the inhibiting class I ligand(s) NK cell alloreactions may occur. Donor versus recipient NK alloreactions occur in full HLA haplotype-mismatched ("haploidentical") hematopoietic transplants that are KIR ligand mismatched in the Graft-versus-Host (GvH) direction. Variable frequencies of functional NK cells in the donor repertoire expressing a KIR for the HLA class I group which is absent in the recipient as their sole inhibitory receptor for self, sense the missing expression of the self class I ligand on allogeneic targets and mediate alloreactions ("missing self" recognition). In clinical trials, donor versus recipient NK alloreactions are highly beneficial as they reduce the risk of leukemia relapse, do not cause GvHD and markedly improve event-free survival.
人类自然杀伤（NK）细胞功能受一类克隆性分布的抑制性受体调控，这类受体被称为“杀伤细胞免疫球蛋白样受体”（KIRs），它们识别由HLA - C和HLA - B I类等位基因组共享的表位（“KIR配体”），并且库中的每个功能性NK细胞都表达至少一种针对自身HLA - I类分子的受体。因此，当NK细胞遇到不表达抑制性I类配体的异基因靶标时，可能会发生NK细胞同种异体反应。供体对受体的NK同种异体反应发生在完全HLA单倍型不匹配（“单倍体相合”）的造血移植中，这些移植在移植物抗宿主（GvH）方向上存在KIR配体不匹配。供体库中表达针对受体中不存在的HLA - I类组的KIR的功能性NK细胞频率各异，这些KIR作为它们唯一的自身抑制性受体，感知到异基因靶标上自身I类配体的缺失表达并介导同种异体反应（“缺失自我”识别）。在临床试验中，供体对受体的NK同种异体反应非常有益，因为它们降低了白血病复发的风险，不会引起移植物抗宿主病（GvHD），并显著提高无事件生存率。
