C1:
Allotypic epitopes (allotopes) originating from genetic variation within a species involving different alleles encoding the constant regions of heavy and kappa light chain loci (allotopes are not found on lambda light chains). Because of this polymorphism, IgG allotopes from any given individual are not present in all individuals, and patients receiving 'non-self' IgG (e.g. pooled IgG preparations or blood transfusions) may react with anti-allotypic responses. This is also the case, when patients are 'immunized' with recombinant constructs involving human IgG constant regions.

C2:
Idiotypic epitopes - idiotopes - in the (hyper)variable regions. These idiotopes are usually specific for the individual antibody clone - private idiotopes. Since idiotopes specific for anti-TNF molecules are usually not found in humans, idiotopes on anti-TNF drugs (including 100% human anti-TNF drugs) may be immunogenic.