title: On the origins of adaptive immunity: innate immune receptors join the tale.
abstract: Among members of the Ig superfamily (IgSF), antigen receptors have the unique capacity to rearrange their variable domains, thereby creating an extensive repertoire for antigen recognition. It is assumed that antigen receptors evolved from a non-rearranging IgSF member by insertion of a transposable element. Although the nature of this predecessor is unknown, two multigene families of innate immune receptors that bear a close structural resemblance to antigen receptor chains have been identified in mammals and bony fish, respectively: signal-regulatory proteins (SIRPs) and novel immune-type receptors (NITRs). Members of both families encode V-set Ig domains with a typical antigen receptor-like joining (J) motif and possess the potential to signal through immunoreceptor tyrosine-based inhibition motifs (ITIMs) or immunoreceptor tyrosine-based activation motifs (ITAMs). By analogy to the T-cell receptor (TCR) and certain innate receptors [e.g. killer cell inhibitory receptors (KIRs)] that recognize MHC molecules, SIRP members regulate immune function by interaction with broadly expressed 'self' ligands. We propose the existence of an evolutionary and functional link between innate and adaptive immune receptors that sheds light on the nature of the antigen receptor predecessor(s).
authors.affiliation: Department of Molecular Cell Biology, VU Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. t.vandenberg@vumc.nl
authors.forename: Timo K
authors.initials: TK
authors.lastname: van den Berg
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Yoder
authors.forename: Gary W
authors.initials: GW
authors.lastname: Litman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation; D019143:Evolution, Molecular; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D005810:Multigene Family; D039842:Neural Cell Adhesion Molecule L1 / Q000276:immunology; D011946:Receptors, Antigen; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic; D017386:Sequence Homology, Amino Acid
chemical_list: D000943:Antigens, Differentiation; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D011946:Receptors, Antigen; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic