Amino acid sequence determination of three monoclonal antibodies to angiotensin II

To relate the immunochemical specificity of three murine monoclonal antibodies directed against the octapeptide hormone angiotensin II (AII) to their primary structure, we have sequenced mRNA for the variable regions of their heavy and light chains. Comparison of the sequences indicates that each of the antibodies utilize very closely related V genes in both heavy and light chains. Two of these antibodies, ICH2 and ICA10, display an epitope preference for the carboxy terminus of AII. A third monoclonal antibody, KAA8, displays a lesser specificity for the carboxy terminus of AII than either ICH2 or ICA10. This antibody differs in sequence from the others mainly in the light chain complementarity determining regions (CDR) 1 and 3 and in CDR 3 (D region) on the heavy chain. We interpret these sequence differences as the basis for the observed specificity preferences.