Confirmation of cross-reactivity between Lyme antibody H9724 and human heat shock protein 60 by a combinatorial approach.
A library of Ac-XXXXXPAPRM decapeptides was prepared on a TentaGel solid support using the approach of split synthesis and the strategy of partial chain termination. Epitope screening of the library (17(5) approximately 1.4 x 10(6) decapeptides) with a Lyme monoclonal antibody (H9724) and subsequent MALDI-MS analysis of candidate peptides from colored beads revealed a consensus structure of Xi-DLSXj (Xi = V, L, Y; Xj = G, R). These identified sequences presented no homology to the natural epitope from Borrelia burgdorferi flagellin. However, they were found to resemble a fragment at the N-terminus of human heat shock protein (Hsp60). Our results confirmed that H9724 cross-reacts between bacterial and human proteins and provided support for an autoimmunity mechanism of Lyme disease.
Yu
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Department of Chemistry, Ohio State University, Columbus 43210, USA.
Tu
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Chu
Y H
YH
D000907:Antibodies, Bacterial / Q000276:immunology*; D015748:Borrelia burgdorferi Group / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D003429:Cross Reactions; D018604:Epitope Mapping; D006801:Humans; D066298:In Vitro Techniques; D008193:Lyme Disease / Q000276:immunology*; D010443:Peptide Chain Termination, Translational; D019151:Peptide Library; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000907:Antibodies, Bacterial; D018834:Chaperonin 60; D019151:Peptide Library