Evidence for Molecular Mimicry between Human T Cell Epitopes in Rotavirus and Pancreatic Islet Autoantigens

Abstract

In type 1 diabetes, insulin-producing β cells in the islets of the pancreas are destroyed by autoreactive T cells. Rotavirus (RV) has been implicated in the pathogenesis of type 1 diabetes. Peptides in VP7, a major immunogenic protein of RV, have high sequence similarity to T cell epitope peptides in the islet autoantigens tyrosine phosphatase-like insulinoma Ag 2 (IA2) and glutamic acid decarboxylase 65 (GAD65). We aimed to educe evidence for the hypothesis that molecular mimicry with RV promotes autoimmunity to islet autoantigens. Peptides in RV and their sequence-similar counterparts in IA2 and GAD65 were assayed for binding to HLA molecules associated with type 1 diabetes and for the ability to elicit T cell proliferative responses in HLA-typed individuals. T cells expanded or cloned to epitopes in IA2 or RV were then tested for cross-reactivity with these epitopes. Peptides in RV-VP7, similar to T cell epitopes in IA2 and GAD65, bound strongly to HLA-DRB1*04 molecules that confer susceptibility to type 1 diabetes and were also T cell epitopes in humans at risk for type 1 diabetes. The proliferative responses of T cells to the similar peptides in RV and islet autoantigens were significantly correlated. T cells expanded to the IA2 epitope could be restimulated to express IFN-γ by the similar peptide in RV-VP7, and T cell clones generated to this RV-VP7 peptide cross-reacted with the IA2 epitope. Our findings are consistent with the hypothesis that molecular mimicry with RV could promote autoimmunity to islet Ags.

Thymic Deletion and Regulatory T Cells Prevent Antimyeloperoxidase GN

“…[42][43][44][45] Recent interest has focused on the role of Tregs in peripheral tolerance in inactivating autoreactive CD4+ T cells that escaped central deletion. Administration of PC61 mAb to WT mice was associated with a significant increase in the frequency of anti-MPO CD4+ T cells after MPO immunization.…”

Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

“…The interactions of RRV with APC may lead to bystander B and T cell activation. Additionally, the elevated expression of MHC suggests that the presentation of antigen to T cells is enhanced, so the possibility of T cell molecular mimicry remains [10,41]. CD4 + and CD8 + T cells are critical for diabetes development, while B cells contribute to T cell priming [42][43][44][45].…”

Urticaria por frío: serie de casos y revisión del tema

“…Este tipo de reacción se conoce como mimetismo molecular y se ha demostrado como un mecanismo importante en otras enfermedades (35,36). Pacientes con enfermedades infecciosas, como por ejemplo una mononucleosis (24,37), o que han estado expuestos a situaciones que resulten en una producción elevada de IgE, como la picadura de un insecto (38), desarrollan con mayor frecuencia esta enfermedad que la población general y esto pudiera ser explicado en parte por este mecanismo.…”