PRR adjuvants restrain high stability peptides presentation on APCs

Abstract Adjuvants can affect the function of APCs and boost the adaptive immune responses post vaccination. However, whether adjuvants modulate the specificity of immune responses, especially the specificity of immunodominant epitope responses, and the mechanisms of adjuvants regulating antigen processing and presentation remain poorly defined. Here, using overlapping synthetic peptides, we screened the dominant epitopes of Th1 responses in mice post vaccination with different adjuvants and found that adjuvants altered antigen-specific CD4+ T cell immunodominant epitope hierarchy. MHC-II immunopeptidome demonstrates that peptide repertoires presented by APCs are altered by adjuvants significantly. Unexpectedly, no novel peptide presentation was detected post adjuvants treatment, on the contrary, peptides with high binding stability for MHC-II presented in the control group were missing post adjuvant stimulation, especially in the MPLA and CpG group. The low stability peptide presented in adjuvant groups elicited robust T cell responses effectively and formed immune memory. Taken together, our results suggest that adjuvants (MPLA and CpG) restrain high stability peptides presentation instead of revealing cryptic epitopes, which may alter the specificity of the CD4+ T-cell dominant epitope responses. This capacity of adjuvants to modify pMHC stability and antigen-specific T cell immunodominant epitope responses has fundamental implications for the selection of suitable adjuvants in the vaccine design process and the development of epitope vaccines.