Fine specificity and cross-reactivity of monoclonal antibodies to cyclosporine

More than 180 monoclonal antibodies (McAbs) to the cyclic undecapeptide cyclosporine (Cs) have been prepared. Several immunization protocols and antibody screening processes were compared. Two main groups of McAbs recognizing different "sides" of the Cs molecule could be differentiated. The antibodies belonged to the IgG and IgA classes and showed high affinity for Cs (up to 10(-10) -10(-11) mol/l). Based on their ability to discriminate Cs-derivatives modified singly at each of the 11 residues of the Cs molecule, the antigenic recognition pattern of different McAbs was studied at the level of individual residues. Closely related recognition patterns were found in each of the two main McAb groups. The apparent size of the Cs antigenic sites recognized by different McAbs varied from four to ten residues and did not correlate with antibody affinity.