Antibodies raised against peptide fragments of bovine alpha s1-casein cross-react with the native protein, but recognize sites distinct from the determinants on the protein.

Bovine alpha s1-casein (alpha s1-CN) and its peptides 61-110 and 91-110, which contain both T and B cell determinants on alpha s1-CN and can elicit peptide-native protein cross-reactive antibodies, were selected as model antigens to study whether or not the immune response to the peptides is similar to that to the corresponding regions of the native protein, because they both have a similar disordered conformation in solution. Both alpha s1-CN- and peptide 61-110-primed T cells responded to peptides 61-80 and 91-100, but not to peptides 76-95 and 101-110. In addition, T cells immunized with peptide 91-110 were also stimulated by peptide 91-100, but not by peptide 101-110. These results suggest that the location of the T cell determinant was almost the same in alpha s1-CN and its peptides. On the contrary, antibodies raised against alpha s1-CN bound to peptides 76-95 and 91-100, but not to peptides 61-80 nor 101-110, while anti-peptide 61-110 antibodies preferentially reacted with peptides 61-80 and 101-110, and anti-peptide 91-110 antibodies also bound to peptide 101-110 but not to peptide 91-100. These results indicate that the B cell epitopes were not similar between alpha s1-CN and its peptides. This difference may have arisen because the antigen-B cell or T-B interactions required for the development of a specific antibody response occurred in a different manner between alpha s1-CN and its peptides. These findings may be useful for basic studies on immunology, and could also be applied to the design of new peptide vaccines.