Molecular Mimicry in Pathogen Immune Evasion

• Published in: The Journal of immunology (1950) Vol. 212; no. 1_Supplement; pp. 1438 - 1438_4569
• Main Authors: Santambrogio, Laura, Clement, Cristina, Osan, Jaspreet, Becerra, Aniuska, Mota, Ines, Nanaware, Padma, Franco, Alessandra, Stern, Lawrence
• Format: Journal Article
• Language: English
• Published: 01.05.2024
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.212.supp.1438.4569

Molecular mimicry is the immunological mechanism by which pathogen-derived peptides can modulate immune responses due to sequence similarity with self-peptides. Herein, we report molecular mimicry associated with pathogen immune evasion. A quantitative analysis of the immunopeptidome presented by in vivo mycobacteria tuberculosis (MTB)-matured dendritic cells in HLA-DR0101 (DR1) transgenic mice identified an MTB-processed peptide which presented immunosuppressive capability and shared a DR1 core sequence with a human and mouse self-protein. The TB peptide could expand nTreg with generation of immunosuppressive cytokines in DR1 mice and DR1 subjects diagnosed with active or latent TB. In TB-infected patients the tolerogenic TB peptide reduced the inflammatory response generated to a series of immunogenic TB peptides as quantified by the QuantiFERON test. Additionally, the tolerogenic TB peptide presented an MHC-binding core sequence shared by a multitude of pathogens. Our analysis characterizes a pathogen-derived peptide which, through molecular mimicry facilitate immune evasion by activating/inducing nTreg.