Epitope Masking and Immunodominance — Complications in the Selection of Monoclonal Antibodies Against HCG

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Abstract
Spleen cells from Balb/c mice immunized with HCG were subjected to the normal hybridoma procedures. The resulting MCA''s (from 78 clones) were evaluated in radioimmunoassay, haemagglutination and enzyme immunoassay with whole HCG. The RIA analysis was extended to include HCG subunits and intact LH. The .alpha.-chain of HCG was found to be strongly immunodominant, as shown by the very high frequency (46 of 78) of MCA''s directed at the .alpha.-chain epitopes. These antibodies would bind luteinizing hormone as well as HCG. Only 1 of the 78 clones was specific for the B subunit of HCG, in RIA. This clone was later found to be positive for LH in EIA, thus making the derivation of antibodies specific for this B-epitope extremely difficult. Most MCA''s were found to be applicable in the three types of assay systems (48 of 78), but some were compatible in just one or two of the systems. These differences are believed to be due to epitope masking resulting from the way in which the antigen was handled and presented in the different systems.