Recurrent Staphylococcus aureus infections are common, despite robust immune responses. S. aureus infection elicited protective antibody and T cell responses in mice that expressed the Major Histocompatibility Complex (MHC) of the H-2d haplotype, but not H-2b, demonstrating that host genetics drives individual variability. Vaccination with a-toxin or leukotoxin E (LukE) elicited similar antibody and T cell responses in mice expressing H-2d or H-2b, but vaccine-elicited responses were inhibited by concomitant infection in H-2d-expressing mice. These findings suggested that competitive binding of microbial peptides to host MHC proteins determines the specificity of the immunodominant response, which was confirmed using LukE-derived peptide-MHC tetramers. A vaccine that elicited T cell and antibody responses protected mice that expressed H-2d or H-2b, demonstrating that vaccination can overcome MHC-restricted immunodominance. Together, these results define how host genetics determine whether immunity elicted by S. aureus is protective and provide a mechanistic roadmap for future vaccine design.

中文翻译：

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接种疫苗可以克服MHC限制的免疫优势对金黄色葡萄球菌感染的保护性免疫抑制作用。

尽管有强烈的免疫反应，但反复出现金黄色葡萄球菌感染很常见。金黄色葡萄球菌感染在表达H-2d单倍型而不是H-2b的主要组织相容性复合体（MHC）的小鼠中引起保护性抗体和T细胞应答，表明宿主遗传学驱动个体变异。用α-毒素或白细胞毒素E（LukE）接种疫苗可在表达H-2d或H-2b的小鼠中引起相似的抗体和T细胞应答，但在表达H-2d的小鼠中伴随感染可抑制疫苗引起的应答。这些发现表明，微生物肽与宿主MHC蛋白的竞争性结合决定了免疫显性反应的特异性，这已被LukE衍生的肽-MHC四聚体所证实。引起T细胞和抗体应答的疫苗可保护表达H-2d或H-2b的小鼠，证明疫苗接种可以克服MHC限制的免疫优势。这些结果共同决定了宿主遗传学如何确定金黄色葡萄球菌引起的免疫是否具有保护性，并为未来疫苗设计提供了机械路线图。