Evidence for T Cell Help in the IgG Response against Tandemly RepetitiveTrypanosoma cruziB13 Protein in Chronic Chagas Disease Patients

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.

Down Modulation of Host Immune Response by Amino Acid Repeats Present in a Trypanosoma cruzi Ribosomal Antigen

“…The Leishmania surface proteins A2 ( Fernandes et al, 2014 ), HASP ( Depledge et al, 2010 ), and PSA ( Boceta et al, 2000 ), all of them containing large repeat domains, have been identified as antigens that are strongly recognized by antibodies from infected individuals. Among the T. cruzi surface proteins containing tandemly repeated amino acids known to be targets of the host immune response are B13 antigen ( Duranti et al, 2012 ), TSs ( Freitas et al, 2011 ), mucins ( Giorgi and de Lederkremer, 2011 ), and the mucin-associated surface protein (MASP) ( dos Santos et al, 2012 ). A sub-group of the TS protein family, which is encoded by the largest T. cruzi gene family, with more than 1,000 copies in the parasite genome ( El-Sayed et al, 2005 ; Dc-Rubin and Schenkman, 2012 ), contains at its C-terminal region a amino acid repeat domain known as shed acute phase antigen (SAPA).…”