Epitope Mapping and MHC Restriction of Next-Generation Tuberculosis Vaccine Antigens in Mice

Background/Objectives: Classical major histocompatibility complex (MHC)-restricted T cells play essential roles in tuberculosis (TB) immunity. Characterizing the antigen targets, dominant epitopes, and MHC restriction of protective T-cell responses is important for understanding TB immunity and next-generation TB vaccine development. Methods: We recently used vaccine screening in mice to identify Rv1387 (PPE20), Rv0287 (EsxG), Rv1788 (PE18), and Rv1886c (Ag85B) as protective antigens, and in this paper, characterized the T-cell responses to these antigens in mice. Results: We first identified the full repertoire of CD4 and CD8 T-cell epitopes in C57BL/6 and BALB/c mice. We further defined the MHC class I and II restriction of immunodominant epitopes, enabling the development and validation of tetramers for probing cognate T-cell responses. Finally, we used these tetramers to contrast lung mucosal T-cell phenotypes in the setting of Bacillus Calmette–Guérin (BCG) and mRNA vaccination. Conclusions: These results define the T-cell epitopes and MHC restriction of next-generation TB vaccine antigens and contribute reagents for studying TB T-cell immunity.