Abstract
The tandemly repetitive Trypanosoma cruzi B13 protein is an immunodominant antigen among Chagas disease patients. Such repetitive domains may behave as T-independent antigens. However, T cells can recognize B13 epitopes in an HLA class II-restricted fashion and could potentially provide cognate T cell help and boost antibody titers. We assessed whether the presence of HLA class II molecules able to present B13 epitopes to T cells could affect anti-B13 IgG levels in a cognate fashion, in both major clinical forms of chronic Chagas disease. We found no difference between anti-B13 IgG antibody levels between patients carrying HLA class II molecules associated to T cell responses or other alleles. The predominant anti-B13 IgG subclass was IgG1, with negligible IgG2, suggesting a T-dependent, noncognate help for antibody production. In addition, the finding of increased anti-B13 IgG levels in sera from CCC patients indicates that clinical presentation is associated with increased anti-B13 antibody levels.
Highlights
Pathogenic protozoa like Trypanosoma cruzi, the causative agent of Chagas’ disease, contain regions of tandemly repetitive amino acid sequences embedded in several immunodominant protein antigens [1]
We further stratified the subjects in our study separating them into the two clinical forms of Chagas disease, chronic Chagas’ disease cardiomyopathy (CCC) (n = 32) and asymptomatic/indeterminate form (ASY)
We further analyzed the magnitude of IgG responses and IgG subclasses to the T. cruzi tandemly repetitive B13 antigen in Chagas patients
Summary
Pathogenic protozoa like Trypanosoma cruzi, the causative agent of Chagas’ disease, contain regions of tandemly repetitive amino acid sequences embedded in several immunodominant protein antigens [1]. The function of this type of protein domains is poorly understood. It is known that the repetitiveness of a variety of agents causes MHC class IIindependent, T cell independent activation of B cells, and it has been shown that tandemly repetitive carbohydrate antigens elicit IgG2 subclass antibody responses in humans [4,5,6]. B13 protein is an immunodominant recombinant antigen which encodes part of the tandemly repeated domain of the T. cruzi 140/116 kDa protein located on the surface of infective trypomastigotes from several strains. B13 protein is recognized by IgG serum antibodies from 97% of T. cruzi infected individuals
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