Cell Communication-mediated Nonself-Recognition and -Intolerance in Representative Species of the Animal Kingdom

Werner A. Mueller, Baruch Rinkevich

Research output: Contribution to journalArticlepeer-review


Why has histo-incompatibility arisen in evolution and can cause self-intolerance? Compatible/incompatible reactions following natural contacts between genetically-different (allogeneic) colonies of marine organisms have inspired the conception that self–nonself discrimination has developed to reduce invasion threats by migratory foreign germ/somatic stem cells, in extreme cases resulting in conquest of the whole body by a foreign genome. Two prominent model species for allogeneic discrimination are the marine invertebrates Hydractinia (Cnidaria) and Botryllus (Ascidiacea). In Hydractinia, self–nonself recognition is based on polymorphic surface markers encoded by two genes (alr1, alr2), with self recognition enabled by homophilic binding of identical ALR molecules. Variable expression patterns of alr alleles presumably account for the first paradigm of autoaggression in an invertebrate. In Botryllus, self–nonself recognition is controlled by a single polymorphic gene locus (BHF) with hundreds of codominantly expressed alleles. Fusion occurs when both partners share at least one BHF allele while rejection develops when no allele is shared. Molecules involved in allorecognition frequently contain immunoglobulin or Ig-like motifs, case-by-case supplemented by additional molecules enabling homophilic interaction, while the mechanisms applied to destroy allogeneic grafts or neighbors include taxon-specific tools besides common facilities of natural immunity. The review encompasses comparison with allorecognition in mammals based on MHC-polymorphism in transplantation and following feto-maternal cell trafficking.

Original languageEnglish
Pages (from-to)482-500
Number of pages19
JournalJournal of Molecular Evolution
Issue number6
StatePublished - 1 Aug 2020
Externally publishedYes

Bibliographical note

Funding Information:
We thank Prof. Uri Frank, University of Galway, for proof-reading an earlier version of the manuscript and Prof. Matthew Nicotra, University of Pittsburgh, for advice to correct Fig.?5 a.

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.


  • Allorecognition
  • Auto-aggression
  • Evolutionary immunology
  • Immunological intolerance
  • Self–nonself discrimination

ASJC Scopus subject areas

  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology


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