Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109.
Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109
Proc Natl Acad Sci U S A. 2019 Sep 3;116(36):17951-17956. doi: 10.1073/pnas.1905943116. Epub 2019 Aug 16.
Cluster of differentiation 8 (CD8) is a cell surface glycoprotein, which is expressed as 2 forms, αα homodimer or αβ heterodimer. Peptide-loaded major histocompatibility complex class I (pMHC-I) molecules are major ligands for both forms of CD8. CD8αβ is a coreceptor for the T cell receptor (TCR) and binds to the same cognate pMHC-I as the TCR, thus enabling or augmenting T cell responses. The function of CD8αα homodimers is largely unknown. While CD8αβ heterodimer is expressed exclusively on CD8 T cells, the CD8αα homodimer is present in subsets of T cells and human natural killer (NK) cells. Here, we report that the CD8αα homodimer functions as a coreceptor for KIR3DL1, an inhibitory receptor of NK cells that is specific for certain MHC-I allotypes. CD8αα enhances binding of pMHC-I to KIR3DL1, increases KIR3DL1 clustering at the immunological synapse, and augments KIR3DL1-mediated inhibition of NK cell activation. Additionally, interactions between pMHC-I and CD8αα homodimers regulate KIR3DL1 NK cell education. Together, these findings reveal another dimension to the modulation of NK cell activity.
CD8 是一种细胞表面糖蛋白，有两种形式，即 αα 同源二聚体或 αβ 异源二聚体。负载肽的主要组织相容性复合体 I 类分子（pMHC-I）是这两种形式的 CD8 的主要配体。CD8αβ 是 T 细胞受体（TCR）的辅助受体，与 TCR 结合相同的同源 pMHC-I，从而增强或增强 T 细胞反应。CD8αα 同源二聚体的功能在很大程度上是未知的。虽然 CD8αβ 异源二聚体仅在 CD8 T 细胞上表达，但 CD8αα 同源二聚体存在于 T 细胞和人类自然杀伤 (NK) 细胞的亚群中。在这里，我们报告 CD8αα 同源二聚体作为 NK 细胞抑制受体 KIR3DL1 的辅助受体发挥作用，该受体特异性识别某些 MHC-I 同种型。CD8αα 增强了 pMHC-I 与 KIR3DL1 的结合，增加了 KIR3DL1 在免疫突触处的聚集，并增强了 KIR3DL1 介导的 NK 细胞激活抑制。此外，pMHC-I 与 CD8αα 同源二聚体之间的相互作用调节 KIR3DL1 NK 细胞的教育。总之，这些发现揭示了 NK 细胞活性调节的另一个维度。
