Fig. 1.

Cartoon depictions of putative assembled T cell receptors (TCR, top of each panel) and transcripts (bottom of each panel) illustrate how vertebrates refashion canonical TCR by incorporating immunoglobulin heavy chain (IgH) variable (V) gene segments. a Canonical αβTCR (alpha chain: α, green; beta chain: β, black) and γδTCR (gamma chain: γ, gold; delta chain: δ, blue) are composed of typical V, (D), and J gene segments; b non-canonical TCR replace Vδ (or Vα) with IgH or IgH-like V regions (purple) to form unique TCR chains [L to R: IgHV gene segments associate with nurse shark TCR Cδ (and rarely TCR Cα); TAILV gene segments, unique to nurse sharks, associate with both TCR Cδ and TCR Cα; and IgH-like Vδ (VHδ) gene segments are found in genomes of all gnathostome vertebrate groups except teleost fish and eutherian mammals (but not nurse sharks); c doubly rearranging NAR-TCR, also unique to cartilaginous fish, are composed of two variable domains that undergo separate RAG-mediated VDJ recombination events—a membrane-distal IgNAR-like V domain (NARV, purple) supported by a membrane-proximal TCR Vδ domain (STCRVδ, red)—associated with TCR Cδ; and d TCRμ, found in monotreme and marsupial mammals, combine IgH-like V gene segments (Vμ, light purple) with TCRδ-like C regions (Cμ, teal). Opossums express two isoforms of the receptor: a long form (TCRμ2.0) containing two variable domains—a membrane-distal domain formed by RAG-recombined Vμ, Dμ, and Jμ gene segments and an invariant, membrane-proximal V_μj domain that is pre-joined in the germline (dark pink); and a short form (TCRμ1.0) composed of a single invariant V_μj domain. Platypus express a single TCRμ isoform containing two variable domains that each undergoes a separate recombination event. Transcripts demonstrate the variable use of IgH and TCR D gene segments by non-canonical receptors [V: variable, D: diversifying, and J: joining gene segments; C: constant region; TAILV: TCR-associated Ig-like V; NAR: nurse shark (or new) antigen receptor; RAG: recombination activating genes]. All Ig and Ig-like V, D, and J gene segments are colored in shades of pink/purple. Figure created with BioRender.com