CDR3 length in antigen-specific immune receptors

Abstract

In both immunoglobulins (Ig) and T cell receptors (TCR), the rearrangement of V, D, and J region sequence elements during lymphocyte maturation creates an enormous degree of diversity in an area referred to as the complementarity determining region 3 (CDR3) loop. Variations in the particular V, D, and J elements used, precise points of recombination, and random nucleotide addition all lead to extensive length and sequence heterogeneity. CDR3 loops are often critical for antigen binding in Igs and appear to provide the principal peptide binding residues in TCRs. To better understand the physical and selective constraints on these sequences, we have compiled information on CDR3 size variation for Ig H, L (κ and λ) and TCR α, β, γ, and δ. Ig H and TCR δ CDR3s are the most variable in size and are significantly longer than L and γ chains, respectively. In contrast, TCR α and β chain distributions are highly constrained, with nearly identical average CDR3 lengths, and their length distributions are not altered by thymic selection. Perhaps most significantly, these CDR3 length profiles suggest that γ/δ TCRs are more similar to Igs than to α/β TCRs in their putative ligand binding region, and thus γ/δ and α/β T cells may have fundamentally different recognition properties.