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首页> 外文期刊>Infection and immunity >CD4+ T Lymphocytes from Calves Immunized withAnaplasma marginale Major Surface Protein 1 (MSP1), a Heteromeric Complex of MSP1a and MSP1b, Preferentially Recognize the MSP1a Carboxyl Terminus That Is Conserved among Strains
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CD4+ T Lymphocytes from Calves Immunized withAnaplasma marginale Major Surface Protein 1 (MSP1), a Heteromeric Complex of MSP1a and MSP1b, Preferentially Recognize the MSP1a Carboxyl Terminus That Is Conserved among Strains

机译：犊牛的CD4 + T淋巴细胞免疫了无缘质膜主要表面蛋白1（MSP1），MSP1a和MSP1b的异聚复合物，可优先识别菌株中保守的MSP1a羧基末端。

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Native major surface protein 1 (MSP1) of the ehrlichial pathogenAnaplasma marginale induces protective immunity in calves challenged with homologous and heterologous strains. MSP1 is a heteromeric complex of a single MSP1a protein covalently associated with MSP1b polypeptides, of which at least two (designated MSP1F1 and MSP1F3) in the Florida strain are expressed. Immunization with recombinant MSP1a and MSP1b alone or in combination fails to provide protection. The protective immunity in calves immunized with native MSP1 is associated with the development of opsonizing and neutralizing antibodies, but CD4+ T-lymphocyte responses have not been evaluated. CD4+ T lymphocytes participate in protective immunity to ehrlichial pathogens through production of gamma interferon (IFN-γ), which promotes switching to high-affinity immunoglobulin G (IgG) and activation of phagocytic cells to produce nitric oxide. Thus, an effective vaccine for A. marginaleand related organisms should contain both T- and B-lymphocyte epitopes that induce a strong memory response that can be recalled upon challenge with homologous and heterologous strains. This study was designed to determine the relative contributions of MSP1a and MSP1b proteins, which contain both variant and conserved amino acid sequences, in stimulating memory CD4+ T-lymphocyte responses in calves immunized with native MSP1. Peripheral blood mononuclear cells and CD4+ T-cell lines from MSP1-immunized calves proliferated vigorously in response to the immunizing strain (Florida) and heterologous strains of A. marginale. The conserved MSP1-specific response was preferentially directed to the carboxyl-terminal region of MSP1a, which stimulated high levels of IFN-γ production by CD4+ T cells. In contrast, there was either weak or no recognition of MSP1b proteins. Paradoxically, all calves developed high titers of IgG antibodies to both MSP1a and MSP1b polypeptides. These findings suggest that in calves immunized with MSP1 heteromeric complex, MSP1a-specific T lymphocytes may provide help to MSP1b-specific B lymphocytes. The data provide a basis for determining whether selected MSP1a CD4+ T-lymphocyte epitopes and selected MSP1a and MSP1b B-lymphocyte epitopes presented on the same molecule can stimulate a protective immune response.
机译：埃希氏菌病原体 Anaplasma marginale 的天然主要表面蛋白1（MSP1）可以诱导受到同种和异种菌株攻击的犊牛的保护性免疫。 MSP1是与MSP1b多肽共价结合的单个MSP1a蛋白的异源复合物，在佛罗里达菌株中表达了其中的至少两个（称为MSP1F1和MSP1F3）。单独或组合使用重组MSP1a和MSP1b进行免疫无法提供保护。用天然MSP1免疫的小牛的保护性免疫与调理和中和抗体的发展有关，但尚未评估CD4 + T淋巴细胞反应。 CD4 + T淋巴细胞通过产生γ-干扰素（IFN-γ）参与对埃希氏菌病原体的保护性免疫，该γ-干扰素促进了向高亲和力免疫球蛋白G（IgG）的转换和吞噬细胞的激活以产生一氧化氮。 。因此，一种有效的 A疫苗。边缘和相关生物应同时包含T淋巴细胞和B淋巴细胞抗原决定簇，这些抗原决定簇可诱导强烈的记忆反应，并可以在同源和异源菌株攻击后被召回。本研究旨在确定包含变体和保守氨基酸序列的MSP1a和MSP1b蛋白在刺激用天然MSP1免疫的小牛的记忆CD4 + T淋巴细胞反应中的相对贡献。 MSP1免疫小牛的外周血单核细胞和CD4 + T细胞系在免疫株（Florida）和 A异源株的反应下迅速增殖。保证金。保守的MSP1特异性应答优先针对MSP1a的羧基末端区域，该区域刺激CD4 + T细胞高水平产生IFN-γ。相反，对MSP1b蛋白的识别很弱或没有。矛盾的是，所有牛犊都针对MSP1a和MSP1b多肽开发了高滴度的IgG抗体。这些发现表明，在用MSP1异聚复合物免疫的犊牛中，MSP1a特异性T淋巴细胞可能对MSP1b特异性B淋巴细胞提供帮助。这些数据为确定所选的MSP1a CD4 + T淋巴细胞表位以及同一分子上呈现的所选MSP1a和MSP1b B淋巴细胞表位是否可以刺激保护性免疫应答提供了基础。

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