Tetramer-guided epitope mapping reveals broad, individualized repertoires of tetanus toxin-specific CD41 T cells and suggests HLA-based differences in epitope recognition

Tetanus toxoid isa routinepositivecontrol antigen for cellularassays.Previousstudies identifiedmultiple 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, indicatingprevalent and rarespecificities.Most antigenicpeptides (85%)werepresented byoneor two class II alleles. For peptides presented by three ormore alleles, truncation studies revealed that some contained multiple epitopes. These results contrast with the perceived notion that tetanus toxoid responsesaredominatedbyuniversalCD41T-cellepitopes.Rather theseresults illustrateheterogeneous T-cell responses for different class II alleles and individual-specific variation of the T-cell repertoire.