Exceptional diversity of allorecognition receptors in a nonvertebrate chordate reveals principles of innate allelic discrimination

• 成果类型: Article
• 署名作者: Valbuena, Henry Rodriguez-; Salcedo, Jorge; De Thier, Olivier; Flot, Jean Francois; Tiozzo, Stefano; De Tomaso, Anthony W.
• 署名单位: University of California System; University of California Santa Barbara; Universite Libre de Bruxelles; Centre National de la Recherche Scientifique (CNRS)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2519372122
• 发表日期: 2025-10-28
• 页码: e2519372122
• 关键词: allorecognition; structural immunology; immunogenetics; innate immunity; evolution immunity; mhc class-i; HISTOCOMPATIBILITY LOCUS; SELF-INCOMPATIBILITY; molecular evolution; cell; RECOGNITION; rejection; protein; coevolution; UROCHORDATE

摘要

Highly polymorphic allorecognition systems have been characterized in numerous invertebrate species, and exhibit discriminatory capabilities reminiscent of vertebrate adaptive immunity. As these systems utilize germline encoded receptors, the mechanisms underlying allelic discrimination are unknown. The invertebrate chordate, Botryllus schlosseri, undergoes a natural transplantation reaction controlled by a highly polymorphic, polygenic locus (called the fuhc) with over 1,000 allelic haplotypes found worldwide. Two individuals are compatible if they share one or both fuhc alleles, and we had found that polymorphic discrimination is due to the integration of signals from two allorecognition receptors encoded within the fuhc locus, called fester and uncle fester. Here we show that these two receptors are members of an extended family consisting of diverse gene family, the fester coreceptors (FcoR). Both FF and FcoR are Immunoglobulin motifs, including ITIMs or hemITAMs. FF and FcoR are expressed and encoded as cognate pairs in two polymorphic haplotypes: one within the fuhc locus, and another on a separate chromosome, and remarkably, copy number variation between haplotypes alternative splicing, suggesting that dynamic tuning of activating and inhibitory signand recurring convergent evolution of allorecognition receptors observed from invertebrates to mammals.