The Innate Biologies of Adaptive Antigen Receptors

Adrian C. Hayday*, Pierre Vantourout

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


Nonclonal innate immune responses mediated by germ line-encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line-encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γdelta T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγdelta can make innate and adaptive responses with distinct functional outcomes. Given that αβ T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/beta chains.

Original languageEnglish
Pages (from-to)487-510
Number of pages24
JournalAnnual Review of Immunology
Issue number1
Publication statusPublished - 26 Apr 2020


  • butyrophilins
  • immunoglobulins
  • preparedness
  • superantigens
  • T cell receptors
  • tonic signaling


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