Xu Honglin, Chun Taehoon, Choi Hak-Jong, Wang Bin, Wang Chyung-Ru
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
J Exp Med. 2006 Feb 20;203(2):449-59. doi: 10.1084/jem.20051866. Epub 2006 Feb 13.
The major histocompatibility complex (MHC) class Ib molecule H2-M3 primes the rapid expansion of CD8+ T cells by presenting N-formylated bacterial peptides. However, the significance of H2-M3-restricted T cells in host defense against bacteria is unclear. We generated H2-M3-deficient mice to investigate the role of H2-M3 in immunity against Listeria monocytogenes (LM), a model intracellular bacterial pathogen. H2-M3-deficient mice are impaired in early bacterial clearance during primary infection, with diminished LM-specific CD8+ T cell responses and compromised innate immune functions. Although H2-M3-restricted CD8+ T cells constitute a significant proportion of the anti-listerial CD8+ T cell repertoire, the kinetics and magnitude of MHC class Ia-restricted T cell responses are not altered in H2-M3-deficient mice. The fact that MHC class Ia-restricted responses cannot compensate for the H2-M3-mediated immunity suggests a nonredundant role of H2-M3 in the protective immunity against LM. Thus, the early H2-M3-restricted response temporally bridges the gap between innate and adaptive immune responses, subsequently affecting the function of both branches of the immune system.
主要组织相容性复合体（MHC）I b类分子H2-M3通过呈递N-甲酰化细菌肽引发CD8 + T细胞的快速扩增。然而，H2-M3限制性T细胞在宿主抗细菌防御中的意义尚不清楚。我们构建了H2-M3缺陷小鼠，以研究H2-M3在抗单核细胞增生李斯特菌（LM，一种典型的细胞内细菌病原体）免疫中的作用。H2-M3缺陷小鼠在初次感染期间的早期细菌清除方面存在缺陷，其LM特异性CD8 + T细胞反应减弱，固有免疫功能受损。尽管H2-M3限制性CD8 + T细胞在抗李斯特菌CD8 + T细胞库中占很大比例，但在H2-M3缺陷小鼠中，MHC I a类限制性T细胞反应的动力学和强度并未改变。MHC I a类限制性反应无法补偿H2-M3介导的免疫这一事实表明，H2-M3在抗LM保护性免疫中具有非冗余作用。因此，早期的H2-M3限制性反应在时间上弥合了固有免疫和适应性免疫反应之间的差距，随后影响免疫系统两个分支的功能。
