scVDJ-seq uncovered the rules for CDR3 length pairing in TCR beta and alpha chains as well as BCR heavy and light chains in humans and mice

The binding of T cell receptor (TCR) complementarity determining region 3 (CDR3) or B cell receptor (BCR) CDR3 to antigenic epitopes is essential for adaptive immune responses. However, analyzing the pairing rules of CDR3 lengths-between the beta (β) and alpha (α) chains (or heavy and light chains)-during germline V(D)J recombination and selection processes has long posed a major challenge for immunologists. In this study, we used scVDJ-seq data from public databases to investigate three key aspects at the single T or B cell level: the length distribution range of CDR3, the pairing rules of CDR3, and the pairing differences between the two polypeptide chains of CDR3 in TCR or BCR. Our primary finding reveals that CDR3 pairing conforms to a fundamental rule, wherein the β chain (or heavy chain) is generally longer than the α chain (or light chain). Notably, the difference in length pairing between BCR heavy chain and light chain CDR3 is significantly greater than that between TCR β chain and α chain CDR3. This study offers novel insights into the structural and molecular mechanisms underlying T or B cell responses to antigens.