Natural Exposure to Cutaneous Anthrax Gives Long-Lasting T Cell Immunity Encompassing Infection-Specific Epitopes
Natural Exposure to Cutaneous Anthrax Gives Long-Lasting T Cell Immunity Encompassing Infection-Specific Epitopes
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DOI：
10.4049/jimmunol.0901581
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发表时间：
2010-04-01
影响因子：
4.4
通讯作者：
Altmann, Daniel M.
中科院分区：
文献类型：
--
作者：
Ingram, Rebecca J.;Metan, Goekhan;Altmann, Daniel M.
定义T细胞表位以追踪病毒免疫并设计合理的疫苗已经有很长的历史，但细菌感染的这种类型的数据很少。炭疽杆菌是炭疽病的病原体，是许多地区的地方病病原体，也是一种潜在的生物战威胁。自然感染的炭疽患者的T细胞免疫以前没有被表征，这是令人惊讶的考虑到炭疽毒素破坏或消除适应性免疫的能力。我们调查了土耳其开塞利地区曾感染皮肤炭疽的患者的CD 4 T细胞反应。回答B。从蛋白质水平、结构域水平和表位水平研究了炭疽保护性抗原和致死因子（LF）。在抗生素治疗炭疽感染几年后，可以检测到强烈的T细胞记忆，没有证据表明特异性免疫力受到了预期的损害。虽然现有的炭疽疫苗的血清学反应主要集中在保护性抗原，在感染的个人和炭疽疫苗接种的捐助者的T细胞免疫的主要目标是LF，特别是域IV。这些炭疽抗原表位中的一些表现出广泛的结合几个HLA类等位基因，但其他人在他们的HLA结合模式更受限制。在LF结构域IV内靶向的特异性CD 4 T细胞表位中，一个优先在细菌感染的背景下看到，而不是疫苗接种，这表明这种类型的研究在理解人类免疫系统如何面对严重的细菌感染方面将是重要的。免疫学杂志，2010，184：3814-3821。
There has been a long history of defining T cell epitopes to track viral immunity and to design rational vaccines, yet few data of this type exist for bacterial infections. Bacillus anthracis, the causative agent of anthrax, is both an endemic pathogen in many regions and a potential biological warfare threat. T cell immunity in naturally infected anthrax patients has not previously been characterized, which is surprising given concern about the ability of anthrax toxins to subvert or ablate adaptive immunity. We investigated CD4 T cell responses in patients from the Kayseri region of Turkey who were previously infected with cutaneous anthrax. Responses to B. anthracis protective Ag and lethal factor (LF) were investigated at the protein, domain, and epitope level. Several years after anti biotic-treated anthrax infection, strong T cell memory was detectable, with no evidence of the expected impairment in specific immunity. Although serological responses to existing anthrax vaccines focus primarily on protective Ag, the major target of T cell immunity in infected individuals and anthrax-vaccinated donors was LF, notably domain IV. Some of these anthrax epitopes showed broad binding to several HLA class alleles, but others were more constrained in their HLA binding patterns. Of specific CD4 T cell epitopes targeted within LF domain IV, one is preferentially seen in the context of bacterial infection, as opposed to vaccination, suggesting that studies of this type will be important in understanding how the human immune system confronts serious bacterial infection. The Journal of Immunology, 2010,184: 3814-3821.