T cell epitope characterization in tandemly repetitive Trypanosoma cruzi B13 protein

• Published in: Microbes and infection Vol. 7; no. 11; pp. 1184 - 1195
• Main Authors: Abel, Lúcia C.J., Iwai, Leo K., Viviani, Wladia, Bilate, Angelina M., Faé, Kellen C., Ferreira, Renata C., Goldberg, Anna C., Juliano, Luiz, Juliano, Maria A., Ianni, Bárbara, Mady, Charles, Gruber, Arthur, Hammer, Juergen, Sinigaglia, Francesco, Kalil, Jorge, Cunha-Neto, Edecio
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier SAS 01.08.2005; Amsterdam Elsevier; Paris
• Subjects: Amino Acid Sequence; Animals; Antibodies, Protozoan - blood; Antigens, Protozoan - chemistry; Antigens, Protozoan - immunology; B13 protein; Biological and medical sciences; Chagas Disease - immunology; Epitopes, T-Lymphocyte - immunology; Fundamental and applied biological sciences. Psychology; HLA-DQ alpha-Chains; HLA-DQ Antigens - genetics; HLA-DQ Antigens - metabolism; HLA-DR1 Antigen - genetics; HLA-DR1 Antigen - metabolism; HLA-DR2 Antigen - genetics; HLA-DR2 Antigen - metabolism; Humans; Immunodominant antigens; Immunodominant Epitopes; Microbiology; Models, Molecular; Molecular Sequence Data; Protein Binding; Protozoan Proteins - chemistry; Protozoan Proteins - immunology; T cell epitope; Tandemly repetitive proteins; Trypanosoma cruzi; Trypanosoma cruzi - immunology; CPM; CCC; B13 protein; ASY; ECG; N or CTRL; PHA; PBMC; CLIP class II-associated Ii peptide; LPS; Trypanosoma cruzi; SI; EBV; Immunodominant antigens; HA; T cell epitope; Tandemly repetitive proteins; Kinetoplastida; Antigen; Protozoa; Antigenic determinant; T-Lymphocyte; Immunodominance; Protein
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2005.03.033

Proteins containing tandemly repetitive sequences are present in several immunodominant protein antigens in pathogenic protozoan parasites. The tandemly repetitive Trypanosoma cruzi B13 protein is recognized by IgG antibodies from 98% of Chagas' disease patients. Little is known about the molecular mechanisms that lead to the immunodominance of the repeated sequences, and there is limited information on T cell epitopes in such repetitive antigens. We finely characterized the T cell recognition of the tandemly repetitive, degenerate B13 protein by T cell lines, clones and PBMC from Chagas' disease cardiomyopathy (CCC), asymptomatic T. cruzi infected (ASY) and non-infected individuals (N). PBMC proliferative responses to recombinant B13 protein were restricted to individuals bearing HLA-DQA1*0501(DQ7), -DR1, and -DR2; B13 peptides bound to the same HLA molecules in binding assays. The HLA-DQ7-restricted minimal T cell epitope [FGQAAAG(D/E)KP] was identified with an overlapping combinatorial peptide library including all B13 sequence variants in T. cruzi Y strain B13 protein; the underlined small residues G Q A were the major HLA contact residues. Among natural B13 15-mer variant peptides, molecular modeling showed that several variant positions were solvent (TCR)-exposed, and substitutions at exposed positions abolished recognition. While natural B13 variant peptide S15.9 seems to be the immunodominant epitope for Chagas' disease patients, S15.4 was preferentially recognized by CCC rather than ASY patients, which may be pathogenically relevant. This is the first thorough characterization of T cell epitopes of a tandemly repetitive protozoan antigen and may suggest a role for T cell help in the immunodominance of protozoan repetitive antigens.