Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2021 Jun 13;22(12):6330. doi: 10.3390/ijms22126330.
Beta2-microglobulin (B2M) a key component of major histocompatibility complex class I molecules, which aid cytotoxic T-lymphocyte (CTL) immune response. However, the majority of studies of B2M have focused only on amyloid fibrils in pathogenesis to the neglect of its role of antimicrobial activity. Indeed, B2M also plays an important role in innate defense and does not only function as an adjuvant for CTL response. A previous study discovered that human aggregated B2M binds the surface protein structure in , and a similar study revealed that sB2M-9, derived from native B2M, functions as an antibacterial chemokine that binds . An investigation of sB2M-9 exhibiting an early lymphocyte recruitment in the human respiratory epithelium with bacterial challenge may uncover previously unrecognized aspects of B2M in the body's innate defense against . B2M possesses antimicrobial activity that operates primarily under pH-dependent acidic conditions at which B2M and fragmented B2M may become a nucleus seed that triggers self-aggregation into distinct states, such as oligomers and amyloid fibrils. Modified B2M can act as an antimicrobial peptide (AMP) against a wide range of microbes. Specifically, these AMPs disrupt microbe membranes, a feature similar to that of amyloid fibril mediated cytotoxicity toward eukaryotes. This study investigated two similar but nonidentical effects of B2M: the physiological role of B2M, in which it potentially acts against microbes in innate defense and the role of B2M in amyloid fibrils, in which it disrupts the membrane of pathological cells. Moreover, we explored the pH-governing antibacterial activity of B2M and acidic pH mediated B2M amyloid fibrils underlying such cytotoxicity.
β2-微球蛋白（B2M）是主要组织相容性复合体 I 类分子的关键组成部分，有助于细胞毒性 T 淋巴细胞（CTL）免疫反应。然而，大多数关于 B2M 的研究仅关注淀粉样纤维在发病机制中的作用，而忽略了其抗菌活性的作用。事实上，B2M 在先天防御中也起着重要作用，它不仅作为 CTL 反应的佐剂发挥作用。先前的一项研究发现，人聚集的 B2M 结合 表面蛋白结构，类似的研究表明，源自天然 B2M 的 sB2M-9 作为一种抗菌趋化因子，与 结合。对 sB2M-9 在人体呼吸上皮细胞受到细菌刺激时表现出的早期淋巴细胞募集的研究可能揭示了 B2M 在机体先天防御中的以前未被认识到的方面。B2M 具有抗菌活性，主要在依赖 pH 的酸性条件下发挥作用，在此条件下，B2M 和片段化的 B2M 可能成为触发自组装成不同状态（如寡聚体和淀粉样纤维）的核种子。修饰的 B2M 可以作为一种针对广泛微生物的抗菌肽（AMP）。具体而言，这些 AMP 破坏微生物膜，这一特征类似于淀粉样纤维介导的对真核生物的细胞毒性。本研究调查了 B2M 的两种相似但不相同的作用：B2M 的生理作用，它可能在先天防御中对抗微生物；B2M 在淀粉样纤维中的作用，它破坏病理性细胞的膜。此外，我们探讨了 pH 对 B2M 抗菌活性的控制作用，以及酸性 pH 介导的 B2M 淀粉样纤维在这种细胞毒性中的作用。
