Tetramer-guided epitope mapping reveals broad, individualized repertoires of tetanus toxin-specific CD4+ T cells and suggests HLA-based differences in epitope recognition.

Tetanustoxoidisaroutinepositivecontrolantigenforcellularassays.Previousstudiesidentifiedmultiple tetanus toxin (TT) epitopes, including some ‘universal’ epitopes. However, rigorous HLA-restricted study of tetanus toxoid responses is still lacking. In this study, the tetramer-guided epitope mapping approach was used to identify CD41 T-cell epitopes within the TT heavy chain restricted by 10 different class II alleles. Of 106 peptides tested, 52 contained epitopes. Response frequencies toward specific epitopes varied,indicatingprevalentandrarespecificities.Mostantigenicpeptides(85%)werepresentedbyoneor two class IIalleles. Forpeptidespresentedbythreeor morealleles, truncationstudiesrevealedthatsome contained multiple epitopes. These results contrast with the perceived notion that tetanus toxoid responsesaredominatedbyuniversalCD41T-cellepitopes.Rathertheseresultsillustrateheterogeneous T-cell responses for different class II alleles and individual-specific variation of the T-cell repertoire.