Identification of a human immunodominant T-cell epitope of mycobacterium tuberculosis antigen PPE44

BMC Microbiology

Research Article

Giulia Freer¹  Laura Rindi¹  Barbara Cuccu¹  Alessandro Genovesi¹  Carlo Garzelli¹ 

[1] Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università di Pisa, I-56127, Pisa, Italy;

关键词: Tuberculosis;    Tuberculin Skin Test;    Subunit Vaccine;    Immunological Diagnosis;    Promiscuous Peptide;   

DOI  :  10.1186/1471-2180-11-167

 received in 2011-02-23, accepted in 2011-07-25,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundRecently our group has identified a novel antigen of Mycobacterium tuberculosis, protein PPE44, belonging to the "PPE protein" family. Although its role in infection is largely unknown, PPE44-specific immune responses were detected in mice infected with M. tuberculosis; moreover, immunization of mice with PPE44 subunit vaccines resulted in protective efficacy comparable to the one afforded by BCG against M. tuberculosis (Romano et al., Vaccine 26, 6053-6063, 2008).ResultsIn the present paper, we investigated anti-PPE44 T-lymphocyte responses during human infection by evaluating the frequency of PPE44-specific interferon (IFN)-γ-secreting cells by ELISpot and flow cytometry in a small cohort of healthy subjects that had proven positive to PPD (PPD+) in vitro, in patients with active tuberculosis, in subjects vaccinated with BCG and in unvaccinated, PPD- healthy controls. We showed IFN-γ+ T cell immune responses to recombinant PPE44 in at least a very high proportion of PPD+ individuals tested and, to a lower extent, in subjects vaccinated with BCG. By the use of a panel of overlapping synthetic 20-mer peptides spanning the PPE44 primary amino acid sequence, we identified a strong CD4+ T-cell epitope, encompassed by peptide p1L (VDFGALPPEVNSARMYGGAG), in the NH2-terminus of the PPE44 molecule at the amino acid position 1-20. Conversely, our experiments did not provide evidence of a significant IFN-γ+ CD4+ T cell response to PPE44 or its immunodominant peptide p1L in most (7 out of 8) patients with active TB.ConclusionsOur data suggest an important immunological role of PPE44 and its immunodominant epitope p1L that could be useful in the design of anti-tuberculosis vaccines and in the immunological diagnosis of M. tuberculosis infection.

【 授权许可】

Unknown   
© Cuccu et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.