Modulation of T cell Receptor Repertoire in Autoimmunity after Treatment with Cell Derived Nanoparticles

In this B06 project, we will investigate how the introduction of xenogeneic epitopes can influence T cell responses and influence disease progression in a mouse model of epidermolysis bullosa acquisita (EBA), an autoimmune skin-blistering disease. Specifically, we will analyze the impact of pretreatments with cell-derived nanoparticles (CDNPs), containing a broad spectrum of intracellular proteins, on CD4+ T cell repertoire diversity, T cell polarization, and germinal center (GC) activity.

Previously, our group demonstrated that repeated pretreatment with ovalbumin, a xenogeneic antigen, significantly suppressed EBA disease severity without altering the circulating or skin-binding levels of pathogenic COL7-specific IgG subclasses. This was accompanied by increased Tfh clonotype diversity and an anti-inflammatory IgG glycosylation pattern, suggesting enhanced immune tolerance driven by clonal competition.

Building on these findings, we now employ CDNPs derived from pig and murine cell lines as a source of higher number of epitopes, hypothesizing that these particles further broaden T cell repertoire diversity and favor Th2 polarization. Using an active immunization-induced EBA models, we will compare the T cell receptor (TCR) β-chain sequences and T cell profiles from draining lymph nodes of treated and untreated mice.

We will combine high-throughput TCR sequencing with flow cytometry to uncover the mechanisms by which CDNPs may drive a highly protective immune modulation and reduce autoimmune pathology, offering new insights for antigen-based preventive strategies in autoimmune diseases like EBA.