Proteins that are Very Different from Self

Proteins that are not present in the mammalian genome, such as keyhole limpet haemocyanin, are highly immunogenic. This is to be expected because the great majority of peptides (after proteolytic processing by antigen-presenting cells) will be seen as nonself by T cells, and most of the surface of the protein will be perceived as foreign by B cells. Keyhole limpet haemocyanin is therefore a very effective carrier for immunization with smaller haptenic molecules such as peptides, drugs, hormones or vitamins.

When the corresponding gene is present in the recipient genome, the strength of response will depend on the degree of sequence difference between self and the immunizing protein. As a very rough rule of thumb, proteins from two distant mammalian species, such as mice and humans, might be expected to be about 80% identical in their protein sequences. In other words, about 20% of amino acids might differ between these species in a typical protein. Such differences are very easily detected by the immune system, and numerous antigenic determinants would be recognized.

Occasionally, one finds that immunization with foreign antigens may provoke an antiself response, particularly if complete Freund's adjuvant is used. One such example is the production of autoantibodies to the acetylcholine receptor that develop when rats are immunized with the corresponding protein from electric eels (Lennon et al., 1975; Lindstrom et al., 1988). In this case, it is easy to see how the rat T cells would provide help, as the antigen is clearly foreign. The fact that the rat's B cells are able to respond to self acetylcholine receptor is more difficult to explain, and suggests that in this case, B cells have not been irreversibly tolerized to self during their development.

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