A Trypanosoma cruzi small surface molecule provides the first immunological evidence that Chagas' disease is due to a single parasite lineage.
Chagas' disease is a major health and economic problem caused by the protozoan Trypanosoma cruzi. Multiple independently evolving clones define a complex parasite population that can be arranged into two broad genetic lineages termed T. cruzi I and II. These lineages have different evolutionary origin and display distinct ecological and biological traits. Here we describe a novel molecule termed TSSA for trypomastigote small surface antigen that provides the first immunological marker allowing discrimination between lineages. TSSA is a surface, glycosylphosphatidyl inositol (GPI)-anchored mucin-like protein, highly antigenic during the infection. TSSA sequences from different parasite isolates reveal a population dimorphism that perfectly matches with the two T. cruzi lineages. Interestingly, this dimorphism is restricted to the central region of the molecule, which comprises the immunodominant B cell epitopes. This sequence variability has a major impact on TSSA antigenicity, leading to no immunological cross-reactivity between both isoforms for antibodies present either in immunization or infection sera. Furthermore, the absolute seroprevalence for TSSA in confirmed Chagasic patients is restricted to T. cruzi II isoform, strongly suggesting that human infections are due to this particular subgroup. Even though association of T. cruzi II with Chagas' disease has been proposed based on molecular markers, this is the first immunological evidence supporting this hypothesis. The implications of these results for the future research on Chagas' disease could be envisaged.
Di Noia
Javier M
JM
Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de General San Martín/CONICET, Av. General Paz y Albarellos, San Martin, 1650 Buenos Aires, Argentina.
Buscaglia
Carlos A
CA
De Marchi
Claudia R
CR
Almeida
Igor C
IC
Frasch
Alberto C C
AC
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001118:Argentina; D001483:Base Sequence; D015153:Blotting, Western; D001938:Brazil; D014355:Chagas Disease / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology*; D002677:Chile; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005786:Gene Expression Regulation; D017125:Genes, Protozoan / Q000235:genetics; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D018985:Epitopes, B-Lymphocyte; D007106:Immune Sera; D012333:RNA, Messenger; D014643:Variant Surface Glycoproteins, Trypanosoma; C573505:trypomastigote small surface antigen, Trypanosoma cruzi; C070842:trypomastigote specific surface antigen