Potential role of molecular mimicry between human U1-70 kDa and fungal proteins in the development of T-cell mediated anti-U1-70 kDa autoimmunity

Immunopharmacology and Immunotoxicology
F GuarneriClaudio Guarneri


Molecular mimicry between human and microbial antigens is a possible trigger of autoimmunity. The possible role of this mechanism in the onset of autoimmunity against the human autoantigen U1-70 kDa, typical of mixed connective tissue disease, is not fully elucidated. We aimed to identify microbial proteins highly similar to U1-70 kDa and potentially triggering anti-U1-70 kDa autoimmunity. We compared in silico the amino acid sequence of human U1-70 kDa and those of all the sequenced fungal, viral and bacterial proteins. Human U1-70 kDa shares highly significant (E<10(-20)) amino acid sequence homology, spanning a segment containing T-cell epitopes, with 13 fungal (but no viral or bacterial) proteins, belonging to human pathogens. Nine of these proteins include the amino acid sequence VLVDVERGRTV, identical to the most frequent U1-70 kDa T-cell epitope in anti-U1-70 kDa positive patients, and sequences highly similar to the epitope DAFKTLFVARVN (identical residues or conservative residue substitutions in positions crucial for epitope binding). Cross-reactivity between human U1-70 kDa and microbial proteins was demonstrated for B-cell epitopes, but never investigated before for T-cell epitopes. Our data identify some fungal prot...Continue Reading


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