Ancient Use of Ig Variable Domains Contributes Significantly to the TCR Repertoire.
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The loci encoding B and T cell Ag receptors are generally distinct in commonly studied mammals, with each receptor's gene segments limited to intralocus, cis chromosomal rearrangements. The nurse shark (Ginglymostoma cirratum) represents the oldest vertebrate class, the cartilaginous fish, with adaptive immunity provided via Ig and TCR lineages, and is one species among a growing number of taxa employing Ig-TCR rearrangements that blend these distinct lineages. Analysis of the nurse shark Ig-TCR repertoire found that these rearrangements possess CDR3 characteristics highly similar to canonical TCR rearrangements. Furthermore, the Ig-TCR rearrangements are expressed with TCR, canonically found in the TCR heterodimer. We also quantified BCR and TCR transcripts in the thymus for BCR (IgHV-IgHC), chimeric (IgHV-TCRC), and canonical (TCRV-TCRC) transcripts, finding equivalent expression levels in both thymus and spleen. We also characterized the nurse shark TCR locus with a targeted bacterial artifical chromosome sequencing approach and found that the TCR locus houses a complex of V segments from multiple lineages. An IgH-like V segment, nestled within the nurse shark TCR translocus, grouped with IgHV-like rearrangements we found expressed with TCR (but not IgH) rearrangements in our phylogenetic analysis. This distinct lineage of TCR-associated IgH-like V segments was termed "TAILVs." Our data illustrate a dynamic TCR repertoire employing TCRVs, NARTCRVs, bona fide trans-rearrangements from shark IgH clusters, and a novel lineage in the TCR-associated Ig-like V segments.
