Rapid effector function of circulating NC16A-specific T cells in individuals with mucous membrane pemphigoid

Abstract

Overall, these findings are the first to examine the potential role for antigen-specific autoreactive T cells in the pathogenesis of MMP, and confirm that in some individuals the NC16A domain may be an important target antigen.

Autoreactive T and B Cells from Bullous Pemphigoid (BP) Patients Recognize Epitopes Clustered in Distinct Regions of BP180 and BP230

“…T cell recognition of BP180-NC16A seems to be rather heterogeneous because BP180-NC16A-specific T cell clones from BP patients preferentially expressed TCRBV13, whereas T cell clones derived from a Pg patient expressed TCRBV3 (26). Recently, IFN-␥ secretion by NC16A-specific autoreactive T cells was detected in 2 of 10 patients with MMP and in 2 of 17 patients with BP, but not in healthy controls (27). These results are in apparent contrast to a previous study from our group showing that BP180-reactive T cells from BP patients preferentially secreted Th2-like cytokines, whereas BP180-responsive T cell clones from healthy individuals secreted Th1-like cytokines, such as IFN-␥ (23).…”

“…Previous reports only identified serum autoantibody (10, 21, 33, 34) and autoaggressive T cells (23) recognizing epitopes within the NH 2 -terminal region of the BP180 ECD in the majority of BP patients. Specifically, these studies focused on T cell recognition of the NC16A subdomain, which resides within the NH 2 -terminal region of BP180 (24,25,27,36). In fact, a considerable number of BP and Pg patients studied displayed NC16A-specific peripheral T cell responses, which were mainly of the Th2 type or of a mixed Th1/Th2 type (24,25,27,36).…”

“…Specifically, these studies focused on T cell recognition of the NC16A subdomain, which resides within the NH 2 -terminal region of BP180 (24,25,27,36). In fact, a considerable number of BP and Pg patients studied displayed NC16A-specific peripheral T cell responses, which were mainly of the Th2 type or of a mixed Th1/Th2 type (24,25,27,36). Specifically, Lin et al (24) identified autoreactive T cells directed against the NC16A region of the BP180 ECD in 12 patients with active BP and two patients with Pg.…”

“…Upon proper costimulation, Th cells become activated and secrete distinct cytokines, which stimulate B cells and thus foster plasma cell development and autoantibody production. Autoreactive Th cells that recognize regions of the BP180 ECD, including the immunodominant NC16A region, have been described in selected patients with BP and Pg (23)(24)(25)(26)(27). Clinically, BP has been associated with several MHC class II alleles, HLA-DQB1*0301, -*0305, -*0602, and -*0603 (28).…”

Bioinformatics-Based Predictions of Peptide Binding to Disease-Associated HLA Proteins Suggest Explanation for Shared Autoimmunity

“…72,73 Lastly, the potential role for antigen-specific autoreactive T cells in the pathogenesis of MMP has also been addressed. 74,75 Collectively, these observations suggest that T cell epitopes of the respective autoantigens may bind to their HLA molecules and trigger the activation of autoreactive T cells, which in turn would induce production of pathogenic autoantibodies.…”