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 TCRalpha genes show nucleotide sequence similarities to TCRDdelta segments as high as 89% and show a preponderance of murine TCRDdelta2 or human TCRDdelta3 amino acid sequence similarities. Surprisingly, most of the 5' ends of TCRJgamma segments show nucleotide and amino acid sequence similarities with TCRDbeta segments. All murine and human BCRJH segments and most TCRJdelta segments contain amino acid sequences at their 5' ends that resemble their own D segments, a finding that is not seen with TCRJbeta segments. TCRalpha and TCRgamma 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.