Molecular mimicry by Trypanosoma cruzi: the F1-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide.
Antigenic mimicry by Trypanosoma cruzi antigens that share epitopes with mammalian tissues may drive autoreactive B- or T-cell clones to expand and cause autoimmune pathogenesis. We have been studying one of these antigens, F1-160, a 160-kDa protein on the surface of T. cruzi that antigenically mimics a 48-kDa protein found in mammalian axonal and myenteric plexus cells. The F1-160 antigen has been characterized by cloning and expression of T. cruzi DNA encoding F1-160 in Escherichia coli. Recombinant peptides from various regions of the F1-160 gene were expressed and used to compete with affinity-purified polyclonal anti-F1-160 antibodies binding to nerve. Recombinant 48-amino acid peptide (48X) derived from expression of base pairs 611-761 of the DNA sequence completely inhibited anti-F1-160 binding to nerve. Recombinant peptides expressed from DNA lacking this region did not inhibit anti-F1-160 binding to nerve. Three peptides were synthesized to encompass the 48X peptide, a 12-amino acid peptide and two 18-amino acid peptides. The 12-amino acid peptide TPQRKTTEDRPQ (12X), corresponding to bases 615-651, completely inhibited the binding of anti-F1-160 antibodies to nerve at a concentration of 80 ng/ml (30 microM). The two 18-residue peptides did not inhibit, even at 10 micrograms/ml. Thus, the epitope of F1-160 crossreactive with nervous tissue can be mapped to a 12-amino acid peptide. Some humans with T. cruzi infection make antibodies to F1-160 and to the 48X and 12X peptides. Control sera from uninfected persons did not react with these antigens. Anti-48X antibodies, immunoselected from human serum with 48X peptide, bind to human nerve axons. This demonstrates that some individuals infected with T. cruzi make antibodies to the F1-160 epitope crossreactive with nervous tissues.
Van Voorhis
W C
WC
Department of Medicine, University of Washington, Seattle 98195.
Schlekewy
L
L
Trong
H L
HL
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001666:Binding Sites, Antibody; D014355:Chagas Disease / Q000276:immunology; D003001:Cloning, Molecular; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015345:Oligonucleotide Probes; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D015183:Restriction Mapping; D012584:Sciatic Nerve / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000276:immunology
D000953:Antigens, Protozoan; D000939:Epitopes; D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D009842:Oligopeptides; C069805:FL-160 antigen, Trypanosoma cruzi