Lieto L D, Maasho K, West D, Borrego F, Coligan J E
Receptor Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Genes Immun. 2006 Jan;7(1):36-43. doi: 10.1038/sj.gene.6364268.
CD94/NKG2A is an inhibitory receptor expressed by natural killer (NK) cells and a subset of CD8+ T cells. Ligation of CD94/NKG2A by its ligand HLA-E results in tyrosine phosphorylation of the NKG2A immunoreceptor tyrosine-based inhibitory motifs, and recruitment and activation of the SH2 domain-bearing tyrosine phosphatase-1, which in turn suppresses activation signals. The nkg2a gene encodes two isoforms, NKG2A and NKG2B, with the latter lacking the stem region. We identified three new alternative transcripts of the cd94 gene in addition to the originally described canonical CD94Full. One of the transcripts, termed CD94-T4, lacks the portion that encodes the stem region. CD94-T4 associates with both NKG2A and NKG2B, but preferentially associates with the latter. This is probably due to the absence of a stem region in both CD94-T4 and NKG2B. CD94-T4/NKG2B is capable of binding HLA-E and, when expressed in E6-1 Jurkat T cells, inhibits TCR mediated signals, demonstrating that this heterodimer is functional. Coevolution of stemless isoforms of CD94 and NKG2A that preferentially pair with each other to produce a functional heterodimer indicates that this may be more than a serendipitous event. CD94-T4/NKG2B may contribute to the plasticity of the NK immunological synapse by insuring an adequate inhibitory signal.
CD94/NKG2A是一种由自然杀伤（NK）细胞和一部分CD8 + T细胞表达的抑制性受体。其配体HLA - E与CD94/NKG2A结合会导致NKG2A基于免疫受体酪氨酸的抑制性基序发生酪氨酸磷酸化，并招募和激活含SH2结构域的酪氨酸磷酸酶-1，进而抑制激活信号。nkg2a基因编码两种异构体，即NKG2A和NKG2B，后者缺乏茎区。除了最初描述的经典CD94Full外，我们还鉴定出cd94基因的三种新的可变转录本。其中一种转录本称为CD94 - T4，缺少编码茎区的部分。CD94 - T4与NKG2A和NKG2B都相关联，但优先与后者结合。这可能是由于CD94 - T4和NKG2B都没有茎区。CD94 - T4/NKG2B能够结合HLA - E，并且当在E6 - 1 Jurkat T细胞中表达时，会抑制TCR介导的信号，表明这种异二聚体具有功能。CD94和NKG2A的无茎异构体共同进化，它们优先相互配对以产生功能性异二聚体，这表明这可能不仅仅是一个偶然事件。CD94 - T4/NKG2B可能通过确保足够的抑制信号来促进NK免疫突触的可塑性。
