CDR3 LENGTH IN ANTIGEN-SPECIFIC IMMUNE RECEPTORS

In both immunoglobulins (Ig) and T cell receptors (TCR), the rearrange ment of V, D, and J region sequence elements during lymphocyte maturat ion creates an enormous degree of diversity in an area referred to as the complementarity determining region 3 (CDR3) loop. Variations in th e particular V, D, and J elements used, precise points of recombinatio n, and random nucleotide addition all lead to extensive length and seq uence heterogeneity. CDR3 loops are often critical for antigen binding in Igs and appear to provide the principal peptide binding residues i n TCRs. To better understand the physical and selective constraints on these sequences, we have compiled information on CDR3 size variation for Ig H, L (kappa and lambda) and TCR alpha, beta, gamma, and delta. Ig H and TCR delta CDR3s are the most variable in size and are signifi cantly longer than L and gamma chains, respectively. In contrast, TCR alpha and beta chain distributions are highly constrained, with nearly identical average CDR3 lengths, and their length distributions are no t altered by thymic selection. Perhaps most significantly, these CDR3 length profiles suggest that gamma/delta TCRs are more similar to Igs than to alpha/beta TCRs in their putative ligand binding region, and t hus gamma/delta and alpha/beta T cells may have fundamentally differen t recognition properties.