Immune response to diphtheria toxin and to different CNBr fragments: evidence for different B and T cell reactivities.

The antigenic structure of the diphtheria toxin has been studied in man. B and T cell responses to diphtheria toxoid and to different fragments of the toxin molecule were analyzed in 4 individuals one month after booster immunization. Studies on the B cell response showed that: part of the response was directed against assembled topographic sites; 80% of the response was directed against determinants present on fragment A; the few determinants present on the CNBr peptides of B cross-react with determinants present on A; and reduction of the second disulfide bridge of fragment B diminishes the response. In contrast to the antibody response, most of the T cell reactivity was directed against the B fragment or CNBr peptides from this fragment. Analysis of the fine specificity of T lymphocyte clones revealed that some CNBr fragments share common T cell determinants. These studies indicate that T and B cell determinants are differently distributed on the molecule and that large cross-reactivities that are not explained by the analysis of the amino acid sequence could be found at the B and T cell level.