Morsani College of Medicine, Department of Pediatrics, University of South Florida, Children's Research Institute, St. Petersburg, FL 33701, USA.
Biology and Evolution of Marine Organisms (BEOM), Stazione Zoologica Anton Dohrn, 80122 Naples, Italy.
Philos Trans R Soc Lond B Biol Sci. 2024 May 6;379(1901):20230078. doi: 10.1098/rstb.2023.0078. Epub 2024 Mar 18.
The immune system employs soluble effectors to shape luminal spaces. Antibodies are soluble molecules that effect immunological responses, including neutralization, opsonization, antibody-dependent cytotoxicity and complement activation. These molecules are comprised of immunoglobulin (Ig) domains. The N-terminal Ig domains recognize antigen, and the C-terminal domains facilitate their elimination through phagocytosis (opsonization). A less-recognized function mediated by the C-terminal Ig domains of the IgG class of antibodies (Fc region) involves the formation of multiple low-affinity bonds with the mucus matrix. This association anchors the antibody molecule to the matrix to entrap potential pathogens. Even though invertebrates are not known to have antibodies, protochordates have a class of secreted molecules containing Ig domains that can bind bacteria and potentially serve a similar purpose. The VCBPs (V region-containing chitin-binding proteins) possess a C-terminal chitin-binding domain that helps tether them to chitin-rich mucus gels, mimicking the IgG-mediated Fc trapping of microbes in mucus. The broad functional similarity of these structurally divergent, Ig-containing, secreted effectors makes a case for a unique form of convergent evolution within chordates. This opinion essay highlights emerging evidence that divergent secreted immune effectors with Ig-like domains evolved to manage immune recognition at mucosal surfaces in strikingly similar ways. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.
免疫系统利用可溶性效应分子来塑造腔隙空间。抗体是一种可溶性分子,能够引发免疫反应,包括中和、调理作用、抗体依赖的细胞毒性和补体激活。这些分子由免疫球蛋白 (Ig) 结构域组成。N 端 Ig 结构域识别抗原,C 端结构域则通过吞噬作用(调理作用)促进其清除。IgG 类抗体 C 端 Ig 结构域(Fc 区)介导的一个不太被认可的功能涉及与粘液基质形成多个低亲和力结合。这种结合将抗体分子锚定在基质上,以捕获潜在的病原体。尽管无脊椎动物不被认为具有抗体,但原索动物具有一类含有 Ig 结构域的分泌分子,这些分子可以与细菌结合,并可能具有类似的作用。VCBPs(含 V 区的几丁质结合蛋白)具有 C 端几丁质结合结构域,有助于将其锚定在富含几丁质的粘液凝胶上,模拟 IgG 介导的微生物在粘液中的 Fc 捕获。这些结构上不同但含有 Ig 的分泌效应物具有广泛的功能相似性,这为脊索动物中存在独特形式的趋同进化提供了依据。这篇观点文章强调了一个新兴的证据,即具有 Ig 样结构域的不同分泌免疫效应物进化为以惊人相似的方式在粘膜表面管理免疫识别。本文是主题为“塑造微生物组:宿主因素如何决定和响应微生物定植”的特刊的一部分。