TCRJ and BCRJ gene segments contain 5′ D-segment sequences that contribute to repertoire diversity

Abstract

T cell receptor (TCR) and B cell receptors (BCR) junctions, also known as the CDR3, are where the V, D, and J gene segments converge, coding for a loop structure important for contacting ligands. J segments contribute to the formation of the CDR3 loop through their 5′ ends that vary in length and show high sequence variability. The 5′ ends of J segments of TCRα genes show nucleotide sequence similarities to TCRDδ segments as high as 89% and show a preponderance of murine TCRDδ2 or human TCRDδ3 amino acid sequence similarities. Surprisingly, most of the 5′ ends of TCRJγ segments show nucleotide and amino acid sequence similarities with TCRDβ segments. All murine and human BCRJH segments and most TCRJδ segments contain amino acid sequences at their 5′ ends that resemble their own D segments, a finding that is not seen with TCRJβ segments. TCRα and TCRγ genes thus make up for their lack of separate D segments with distinct D-like segments that are built into the 5′ ends of their J segments. Additionally, in some cases, TCR and BCR genes that utilize separate D segments also receive additional D-like contributions though the 5′ ends of their J segments to add additional diversity to their CDR3 loops.