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dc.contributor.authorOtt, J.A.
dc.contributor.authorOhta, Y.
dc.contributor.authorFlajnik, M.F.
dc.contributor.authorCriscitiello, M.F.
dc.date.accessioned2021-04-12T17:10:13Z
dc.date.available2021-04-12T17:10:13Z
dc.date.issued2021-01-15
dc.identifier.urihttp://hdl.handle.net/10713/15246
dc.description.abstractImmunoglobulins and T cell receptors (TCR) have obvious structural similarities as well as similar immunogenetic diversification and selection mechanisms. Nevertheless, the two receptor systems and the loci that encode them are distinct in humans and classical murine models, and the gene segments comprising each repertoire are mutually exclusive. Additionally, while both B and T cells employ recombination-activating genes (RAG) for primary diversification, immunoglobulins are afforded a supplementary set of activation-induced cytidine deaminase (AID)-mediated diversification tools. As the oldest-emerging vertebrates sharing the same adaptive B and T cell receptor systems as humans, extant cartilaginous fishes allow a potential view of the ancestral immune system. In this review, we discuss breakthroughs we have made in studies of nurse shark (Ginglymostoma cirratum) T cell receptors demonstrating substantial integration of loci and diversification mechanisms in primordial B and T cell repertoires. We survey these findings in this shark model where they were first described, while noting corroborating examples in other vertebrate groups. We also consider other examples where the gnathostome common ancestry of the B and T cell receptor systems have allowed dovetailing of genomic elements and AID-based diversification approaches for the TCR. The cartilaginous fish seem to have retained this T/B cell plasticity to a greater extent than more derived vertebrate groups, but representatives in all vertebrate taxa except bony fish and placental mammals show such plasticity. Copyright 2021, Springer-Verlag GmbH Germany, part of Springer Nature.en_US
dc.description.sponsorshipThis work was supported by grants from the NIH to MFC (AI56963) and MFF (AI027877 and AI140326) and the NSF to MFC (IOS-1257829 and IOS-1656870).en_US
dc.description.urihttps://doi.org/10.1007/s00251-020-01183-5en_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909615/
dc.language.isoen_USen_US
dc.publisherSpringer Science and Business Media Deutschland GmbHen_US
dc.relation.ispartofImmunogenetics
dc.subjectactivation induced cytidine deaminaseen_US
dc.subjectBony fishen_US
dc.subjectevolution: antigen receptor locien_US
dc.subjectImmunoglobulinsen_US
dc.subjectPlacental mammalsen_US
dc.subjectSharken_US
dc.subjectT cell receptorsen_US
dc.subjectVertebrate adaptive immune systemen_US
dc.titleLost structural and functional inter-relationships between Ig and TCR loci in mammals revealed in sharksen_US
dc.typeArticleen_US
dc.identifier.doi10.1007/s00251-020-01183-5
dc.identifier.pmid33449123


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