T cell receptor recognizing Desmoglein 3 peptide–MHC class II complex (Dsg3-specific TCR)

The T cell receptor (TCR) recognizing the Desmoglein 3 (Dsg3) peptide–MHC class II complex is a central driver of the autoimmune pathology in Pemphigus Vulgaris (PV) [1.1.3, 1.2.4]. This receptor is expressed on the surface of autoreactive CD4+ T helper cells and specifically binds to Dsg3 autoantigenic peptides presented by disease-associated MHC class II alleles, most notably HLA-DRB1*04:02 and HLA-DQB1*05:03 [1.3.2, 1.3.3]. This recognition event triggers T cell activation and the secretion of Th2-type cytokines, which provide essential help to B cells for the production of pathogenic anti-Dsg3 IgG autoantibodies [1.1.4, 1.2.5]. These antibodies disrupt desmosomal adhesion between keratinocytes, leading to the characteristic blistering of the skin and mucous membranes [1.3.4]. Because of its specific role in the disease, this TCR is a high-value target for precision therapies like the peptide vaccine PI-0824, which is designed to induce antigen-specific tolerance [1.3.1, 1.3.2]. Such approaches aim to selectively silence the autoreactive immune response without the broad side effects associated with conventional systemic immunosuppressants [1.2.1, 1.3.2].

Other names

Desmoglein 3-specific T cell receptorDsg3-reactive TCRAutoreactive TCR in Pemphigus VulgarisDsg3:MHC II-specific TCR

Induction of antigen-specific T cell tolerance and anergy through TCR-pMHC interaction in the absence of costimulation