Identification of a human immunodominant T-cell epitope of mycobacterium tuberculosis antigen PPE44.
Identification of a human immunodominant T-cell epitope of mycobacterium tuberculosis antigen PPE44.
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DOI：
10.1186/1471-2180-11-167
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发表时间：
2011-07-25
期刊：
影响因子：
4.2
通讯作者：
Rindi L
中科院分区：
文献类型：
--
作者：
Cuccu B;Freer G;Genovesi A;Garzelli C;Rindi L
最近，我们的小组已经确定了一种新的结核分枝杆菌抗原，蛋白PPE 44，属于“PPE蛋白”家族。尽管其在感染中的作用在很大程度上是未知的，但在感染M.肺结核;此外，用PPE 44亚单位疫苗免疫小鼠产生的保护效力与BCG提供的抗M的保护效力相当。结核病（Romano等，Vaccine 26，6053-6063，2008）。在本论文中，我们通过ELISpot和流式细胞术评估体外PPD（PPD+）阳性健康受试者、活动性结核病患者、接种BCG受试者和未接种PPD-健康对照者中PPE 44特异性干扰素（IFN）-γ分泌细胞的频率，研究了人类感染期间抗PPE 44 T淋巴细胞应答。我们显示IFN-γ+ T细胞对重组PPE 44的免疫应答在至少非常高比例的PPD+受试者中，并且在较低程度上，在接种BCG的受试者中。通过使用跨越PPE 44一级氨基酸序列的一组重叠的合成20聚体肽，我们在PPE 44分子的NH 2-末端的氨基酸位置1-20处鉴定了由肽p1 L（VDFGALPPEVNSARMYGGAG）包含的强CD 4 + T细胞表位。相反，我们的实验没有提供证据表明大多数（8例中的7例）活动性TB患者对PPE 44或其免疫显性肽p1 L产生显著的IFN-γ+ CD 4 + T细胞应答。提示PPE 44及其免疫优势表位p1 L具有重要的免疫学作用，可用于抗结核疫苗的设计和结核分枝杆菌的免疫学诊断。肺结核感染。
Recently 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). In 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. Our 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.
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