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首页> 外文期刊>Infection and immunity >Elimination of the listeriolysin O-directed immune response by conservative alteration of the immunodominant listeriolysin O amino acid 91 to 99 epitope.
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Elimination of the listeriolysin O-directed immune response by conservative alteration of the immunodominant listeriolysin O amino acid 91 to 99 epitope.

机译：通过保守免疫为主的李斯特菌溶血素O氨基酸91至99表位的保守改变，消除了李斯特菌溶血素O定向的免疫反应。

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摘要

A major H2-Kd-presented epitope for antilisterial cytotoxic T lymphocytes (CTLs) is the nanomer peptide which corresponds to the amino acid 91 to 99 (aa91-99) sequence from listeriolysin O (LLO). Although the LLO sequence contains at least five additional nanomer peptides which also satisfy the H2-Kd binding motif, aa91-99 is the only LLO-derived target peptide that is recognized by antilisterial CTLs following infection of BALB/c mice with Listeria monocytogenes. In order to investigate further the immunodominance of the LLO aa91-99 epitope following endogenous processing of LLO, we introduced a point mutation in hly (the gene for LLO) which results in a conservative Y-to-F substitution for the anchor residue at position 2 within the aa91-99 sequence. This "92F" L. monocytogenes mutant produces biologically active LLO and is phenotypically indistinct from wild-type L. monocytogenes in terms of intracellular growth in vitro and virulence in vivo. BALB/c mice actively immunized with the 92F L. monocytogenes mutant are protected against challenge with wild-type L. monocytogenes. Antilisterial CTLs from mice immunized with the 92F mutant lyse targets infected with L. monocytogenes; however, these CTLs do not lyse target cells pulsed with either the LLO aa91-99 peptide, other LLO-derived peptides which satisfy the H2-Kd binding motif, or a peptide corresponding to the LLO aa91-92F-99 sequence. Target cells pulsed with the LLO aa91-92F-99 peptide are, however, lysed by wild-type LLO aa91-99-specific cytotoxic cells. Thus, a conservative amino acid change in the first anchor residue of the immunodominant aa91-99 sequence of LLO eliminates the induction of the cytotoxic cell response to this epitope as well as to any of the other candidate LLO-derived peptides which fit the H2-Kd binding motif. The lack of anti-LLO-specific CTLs following immunization with the 92F mutant does not appear, however, to influence the protective antilisterial immune response.
机译：抗李斯特菌细胞毒性T淋巴细胞（CTL）的主要H2-Kd呈递表位是纳米单体肽，它对应于李斯特菌溶血素O（LLO）的氨基酸91至99（aa91-99）序列。尽管LLO序列包含至少五个也满足H2-Kd结合基序的其他纳米单体肽，但aa91-99是唯一的LLO衍生靶肽，在单核细胞增生李斯特菌感染BALB / c小鼠后被抗李斯特氏菌CTL识别。为了进一步研究内源性处理LLO后LLO aa91-99表位的免疫优势，我们在hly中引入了点突变（LLO的基因），该突变导致保守的Y到F取代位置的锚残基2在aa91-99序列内。该“ 92F”单核细胞增生李斯特氏菌突变体产生生物活性的LLO，并且在体外细胞内生长和体内毒力方面与野生型单核细胞增生李斯特氏菌在表型上不清楚。用92F单核细胞增生李斯特氏菌突变体主动免疫的BALB / c小鼠受到保护，免受野生型单核细胞增生李斯特氏菌的攻击。来自用单核细胞增生李斯特菌感染的92F突变裂解靶标免疫的小鼠的抗李斯特氏菌CTL;但是，这些CTL不会裂解被LLO aa91-99肽，满足H2-Kd结合基序的其他LLO衍生肽或对应于LLO aa91-92F-99序列的脉冲后的靶细胞。然而，用LLO aa91-92F-99肽脉冲的靶细胞被野生型LLO aa91-99特异性细胞毒性细胞裂解。因此，LLO的免疫显性aa91-99序列的第一锚定残基中的保守氨基酸改变消除了对该表位以及对任何适合H2-的其他候选LLO-衍生肽的细胞毒性细胞应答的诱导。 Kd结合基序。但是，用92F突变体免疫后，缺乏抗LLO特异的CTL并没有影响保护性抗李斯特菌免疫应答。

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