Molecular mimicry in type 1 diabetes: immune cross‐reactivity between islet autoantigen and human cytomegalovirus but not Coxsackie virus

BO Roep, HS Hiemstra, NC Schloot… - Annals of the New …, 2002 - Wiley Online Library
BO Roep, HS Hiemstra, NC Schloot, RRP De Vries, A Chaudhuri, PO Behan, JW Drijfhout
Annals of the New York Academy of Sciences, 2002Wiley Online Library
Type 1 diabetes is caused by a T cell‐mediated autoimmune destruction of the pancreatic
beta cells. Molecular mimicry between viral pathogens and beta cell protein has been a
popular theory to explain loss of tolerance in type 1 diabetes. However, functional data in
support of this hypothesis have been lacking, presumably because the homologies were
defined on the basis of linear similarities in peptide sequences, which ignores the criteria of
HLA versus T cell receptor contact residues in peptide epitopes required for T cell …
Abstract: Type 1 diabetes is caused by a T cell‐mediated autoimmune destruction of the pancreatic beta cells. Molecular mimicry between viral pathogens and beta cell protein has been a popular theory to explain loss of tolerance in type 1 diabetes. However, functional data in support of this hypothesis have been lacking, presumably because the homologies were defined on the basis of linear similarities in peptide sequences, which ignores the criteria of HLA versus T cell receptor contact residues in peptide epitopes required for T cell recognition. We applied a HLA‐binding dedicated peptide microarray analysis using autoreactive T cell clones specific for the autoantigen GAD65 to determine the algorithm of T cell recognition by this given T cell clone. The subsequent database search identified a 100% fit with cytomegalovirus peptide, which was subsequently shown to be recognized by these clonal T cells. However, T cell clones reactive with linear homologies previously described as putative candidates for T cell cross‐reactivity between GAD65 and Coxsackie virus peptide were unable to recognize the homologous counterparts.
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