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Molecular mimicry by Trypanosoma cruzi: the F1-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide.
Title | Molecular mimicry by Trypanosoma cruzi: the F1-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide. |
Publication Type | Journal Article |
Year of Publication | 1991 |
Authors | Van Voorhis, WC, Schlekewy, L, Trong, HL |
Journal | Proc Natl Acad Sci U S A |
Volume | 88 |
Issue | 14 |
Pagination | 5993-7 |
Date Published | 1991 Jul 15 |
ISSN | 0027-8424 |
Keywords | Amino Acid Sequence, Animals, Antigens, Protozoan, Base Sequence, Binding Sites, Antibody, Chagas Disease, Cloning, Molecular, Cross Reactions, Epitopes, Humans, Mice, Mice, Inbred C3H, Molecular Sequence Data, Nerve Tissue Proteins, Oligonucleotide Probes, Oligopeptides, Polymerase Chain Reaction, Restriction Mapping, Sciatic Nerve, Trypanosoma cruzi |
Abstract | 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. |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 1712477 |