Hierarchic T‐Cell Help to Non‐Linked B‐Cell Epitopes

The induction of antibodies against peptides requires the presence of a T helper cell epitope. In the absence of an added T‐cell epitope only 10% of the mice, or less depending on the strain, gave an antibody response to a series of peptides of the measles virus (MV) fusion (F) protein. After co‐immunization with a non‐covalently coupled T‐cell epitope more than 60% of the peptides became immunogenic. Considerable differences became apparent when BALB/c mice were immunized with peptides in the presence of different T‐cell epitopes. An immunodominant T‐cell epitope of the MV‐F protein was more efficient than a subdominant or a cryptic T‐cell epitope in providing help to a non‐linked B‐cell epitope. There is both a ranking order of the amount of help which B‐cell epitopes require and a ranking order for the help T‐cell epitopes are able to provide. The capability of a T‐cell epitope to provide help to a B‐cell epitope correlated with its own immunogenicity, i.e. the intensity of the antibody response to the peptide representing the T‐cell epitope. The data suggest that for each MHC class II allele there is an optimal T‐cell epitope which can provide help to a maximal number of B‐cell epitopes and that such a peptide can be identified by its ability to induce antibodies against itself. By using this strategy, the authors were able to induce antibodies which cross‐reacted with the MV.