Origins of the RAG transposome and the MHC

Louis Tsakou-Ngouafo, Julien Paganini, Jim Kaufman, Pierre Pontarotti

Research output: Contribution to journalReview articlepeer-review

Abstract

The appearance of adaptive immunity in vertebrates remains unclear, although many proposals have been made. In this speculative review, we describe the complex innate immune systems in place before the emergence of the vertebrates, and propose the existence of a molecule(s) on the surface of some cells able to present pathogen-associated molecular patterns (PAMPs) to a specific receptor(s) on other cells, much like molecules of the major histocompatibility complex (MHC) and T cell receptors (TCRs). Crucially, an MHC-like molecule with a mutation allowing it to recognize a new PAMP would be unlikely to be recognized by the specific TCR-like molecule, and so there would be no selection for the new MHC-like molecule whose gene would then be lost by neutral drift. The integration of the recombination activating gene (RAG) transposon in a TCR-like gene would have led to a significant increase in the recognition possibilities, so that new MHC-like variants could be recognized and selected, along with the new RAG/TCR-like system. The eventual consequence of this scenario would be the ability of the MHC to present many peptides, through multigene families, polymorphism of individual genes and an increase in peptide-binding repertoire (promiscuity).
Original languageEnglish
Pages (from-to)561-571
Number of pages11
JournalTrends in Immunology
Volume41
Issue number7
Early online date25 May 2020
DOIs
Publication statusPublished - 1 Jul 2020

Keywords

  • hairpin
  • flanking
  • DDE transposon excision
  • Artemis
  • palindromic diversity
  • convergent evolution

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