T cell receptor recognizing PVT301-presented disease-specific peptide–MHC class II complexes (TCR)

The T cell receptor (TCR) recognizing PVT301-presented disease-specific peptide–MHC class II complexes is a critical component of the adaptive immune system involved in the pathogenesis of celiac disease [1, 7]. These receptors are expressed on the surface of pathogenic CD4+ T cells and are specifically tuned to recognize deamidated gluten peptides, such as those derived from alpha-gliadin, when presented by MHC class II molecules, primarily HLA-DQ2.5 or HLA-DQ8 [8, 11]. In individuals with celiac disease, the activation of these T cells by dietary gluten triggers a pro-inflammatory cytokine cascade that leads to the destruction of the small intestinal lining and chronic malabsorption [4, 13]. PVT301 is an investigational therapeutic known as a Navacim, which consists of nanoparticles decorated with these specific peptide-MHC class II complexes [1, 2]. When PVT301 interacts with the target TCR, it does not cause typical T cell activation; instead, it induces the differentiation of the pathogenic T cells into Type 1 regulatory T (Tr1) cells [1, 5]. These newly formed Tr1 cells then migrate to the site of inflammation and suppress the localized autoimmune attack, potentially offering a way to restore gluten tolerance without causing broad-spectrum immunosuppression [1, 12].

Other names

Gluten-specific T cell receptorPathogenic CD4+ T cell receptorCeliac disease-associated T cell receptorHLA-DQ2.5-restricted T cell receptorHLA-DQ8-restricted T cell receptor

PVT301 is a Navacim (nanoparticle-peptide-MHC complex) that binds to the specific T cell receptor on pathogenic CD4+ T cells, inducing their differentiation into regulatory T cells (Tr1 cells) to suppress inflammation and restore immune tolerance.