Health Sciences Research Center (CICS-UBI), University of Beira Interior, 6200-506 Covilhã, Portugal.
Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal.
Int J Mol Sci. 2021 Sep 8;22(18):9738. doi: 10.3390/ijms22189738.
Studies carried out during the last few decades have consistently shown that cell surface MHC class I (MHC-I) molecules are endowed with functions unrelated with antigen presentation. These include cis-trans-interactions with inhibitory and activating KIR and LILR, and cis-interactions with receptors for hormones, growth factors, cytokines, and neurotransmitters. The mounting body of evidence indicates that these non-immunological MHC-I functions impact clinical and biomedical settings, including autoimmune responses, tumor escape, transplantation, and neuronal development. Notably, most of these functions appear to rely on the presence in hematopoietic and non-hematopoietic cells of heavy chains not associated with β2m and the peptide at the plasma membrane; these are known as open MHC-I conformers. Nowadays, open conformers are viewed as functional cis-trans structures capable of establishing physical associations with themselves, with other surface receptors, and being shed into the extracellular milieu. We review past and recent developments, strengthening the view that open conformers are multifunctional structures capable of fine-tuning cell signaling, growth, differentiation, and cell communication.
过去几十年的研究一直表明，细胞表面 MHC Ⅰ类（MHC-I）分子具有与抗原呈递无关的功能。这些功能包括与抑制性和激活型 KIR 和 LILR 的顺式-反式相互作用，以及与激素、生长因子、细胞因子和神经递质受体的顺式相互作用。越来越多的证据表明，这些非免疫性 MHC-I 功能会影响临床和生物医学领域，包括自身免疫反应、肿瘤逃逸、移植和神经元发育。值得注意的是，这些功能似乎大多依赖于存在于造血细胞和非造血细胞中的与β2m 无关的重链和位于质膜上的肽；这些被称为开放 MHC-I 构象。如今，开放构象被视为能够与自身、其他表面受体建立物理关联并被释放到细胞外环境中的功能性顺式-反式结构。我们回顾了过去和最近的发展，进一步证实了开放构象是多功能结构，能够精细调节细胞信号转导、生长、分化和细胞通讯。
