Dominant T- and B-cell epitopes in an autoantigen linked to Chagas' disease.
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.
Gironès
N
N
Centro de Biología Molecular, Conrejo Superior de Investigaciones Científicos, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
Rodríguez
C I
CI
Carrasco-Marín
E
E
Hernáez
R F
RF
de Rego
J L
JL
Fresno
M
M
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D014355:Chagas Disease / Q000276:immunology / Q000473:pathology; D003429:Cross Reactions; D016054:DNA, Protozoan; D004198:Disease Susceptibility; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009206:Myocardium / Q000473:pathology; D009439:Neuraminidase / Q000276:immunology; D015800:Protozoan Proteins; D014349:Trypanosoma cruzi / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D001323:Autoantibodies; D001324:Autoantigens; C427103:Cha protein, Trypanosoma cruzi; D016054:DNA, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D016056:Immunodominant Epitopes; D015800:Protozoan Proteins; C069715:trans-sialidase; D009439:Neuraminidase