Abstract
In Chagas' disease caused by Trypanosoma cruzi, a paradigm of autoimmune disease, both autoantibodies and autoreactive T cells have been described. We have identified a novel dominant autoantigen, named Cha, recognized by the majority of sera from T. cruzi-infected humans and mice. We noted significant homologies between amino acids 120-129 of Cha, where the B-cell epitope maps, and an expressed sequence tag from T. cruzi, and also between amino acids 254-273 of Cha and a repeated amino acid sequence from the shed acute-phase antigen (SAPA) of T. cruzi. Moreover, T. cruzi-infected mice contain autoreactive T cells that can cross-react with Cha and the SAPA homologous peptides. Transfer of T cells from infected mice triggered anti-Cha (120-129) Ab production in naive recipients. Interestingly, heart tissue sections from those adoptive transferred mice showed cardiac pathology similar to T. cruzi-infected mice. Our results demonstrate the presence of both T- and B-cell cross-reactive epitopes in the Cha antigen. This dual mimicry may lead to T/B cell cooperation and give rise to a pathological immunodominant response against Cha in T. cruzi infected animals.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Amino Acid Sequence
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Animals
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Antibodies, Protozoan / blood
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Antibodies, Protozoan / immunology
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Antigens, Protozoan / genetics
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Antigens, Protozoan / immunology*
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Autoantibodies / biosynthesis
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Autoantibodies / blood
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Autoantibodies / immunology
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Autoantigens / genetics
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Autoantigens / immunology*
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Base Sequence
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Chagas Disease / immunology
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Chagas Disease / pathology
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Cross Reactions
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DNA, Protozoan
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Disease Susceptibility
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Epitopes, B-Lymphocyte / genetics
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Epitopes, B-Lymphocyte / immunology*
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology*
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Female
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Glycoproteins / immunology
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Humans
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Immunity, Innate
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Immunodominant Epitopes / genetics
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Immunodominant Epitopes / immunology*
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Kinetics
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Molecular Sequence Data
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Myocardium / pathology
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Neuraminidase / immunology
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Protozoan Proteins*
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Trypanosoma cruzi / immunology*
Substances
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Antibodies, Protozoan
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Antigens, Protozoan
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Autoantibodies
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Autoantigens
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Cha protein, Trypanosoma cruzi
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DNA, Protozoan
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Epitopes, B-Lymphocyte
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Epitopes, T-Lymphocyte
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Glycoproteins
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Immunodominant Epitopes
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Protozoan Proteins
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trans-sialidase
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Neuraminidase