CAN IMMUNOGLOBULIN C(H)1 CONSTANT-REGION DOMAIN MODULATE ANTIGEN-BINDING AFFINITY OF ANTIBODIES

Although the switch process is frequently associated with affinity mat uration, the constant region is not assumed to play a role in Ag-Ab bi nding, In the present work, we demonstrate that two clonally related h uman monoclonal Igs sharing identical V-H and V-L sequences, but expre ssing different isotypes (IgA1 kappa(PER) and IgG1 kappa(PER)), bind t ubulin with significantly different affinities, This difference was ma inly accounted for by a disparity in the association rate constants. T hese results suggest that affinity maturation of this clone could be a chieved through class switching in the absence of further somatic muta tions, Since the differences observed were found at the Fab level, the y also suggest a role for the C(H)1 domain in structuring the Ag-bindi ng site into a more kinetically competent form.