Immunopeptidomics analysis of Lyme arthritis: insights into infection and autoimmunity

Abstract

Abstract Background: Lyme arthritis (LA) is caused by infection with the Lyme disease spirochete Borrelia burgdorferi (Bb) and in humans is often accompanied by autoimmune T and B cell responses. In this study, we used an immunopeptidomics approach to gain further insight into mechanisms of infection-induced autoimmunity. Methods: C57BL/6 (B6) mice, which develop mild, self-limiting LA, and B6 Il10−/− mice, which develop chronic, autoimmune-like LA, were inoculated with 2×104 Bb. Inguinal and popliteal lymph nodes (LN) were harvested from infected mice at 4 weeks and 16 weeks post-inoculation. MHC class II molecules were isolated by immunoaffinity capture and MHC-bound peptides were identified by LC/MS/MS. Results: Nearly 10,000 MHCII-bound peptides were identified. At 4 weeks post-inoculation, representing the peak of LA, proteins involved in leukocyte trans-endothelial migration, tissue repair, and immune activation, including a known Lyme autoantigen ApoB-100, were over-represented in both B6 and Il10−/− mice. Peptides from these proteins returned to near baseline levels in LN from B6 mice at 16 weeks post-inoculation, when arthritis resolves, but were further enriched in Il10−/− mice at 16 weeks, during the chronic, autoimmune-like phase. Surprisingly, only 27 peptides derived from Bb proteins were identified, all but one of which were from proteins found in the inner membrane, periplasm, or cytosol. Conclusions: This study identified immune-relevant proteins presented by APCs in draining LN that are associated with LA development, which included ApoB-100, a known Lyme autoantigen in humans. Further studies are underway to assess T cell responses to identified Bb and self-peptides, including ApoB-100, during Bb infection.