Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Eur J Immunol. 2013 Apr;43(4):897-906. doi: 10.1002/eji.201242983. Epub 2013 Feb 18.
Distinct peptide-MHC-II complexes, recognised by Type A and B CD4(+) T-cell subsets, are generated when antigen is loaded in different intracellular compartments. Conventional Type A T cells recognize their peptide epitope regardless of the route of processing, whereas unconventional Type B T cells only recognise exogenously supplied peptide. Type B T cells are implicated in autoimmune conditions and may break tolerance by escaping negative selection. Here we show that Salmonella differentially influences presentation of antigen to Type A and B T cells. Infection of bone marrow-derived dendritic cells (BMDCs) with Salmonella enterica serovar Typhimurium (S. Typhimurium) reduced presentation of antigen to Type A T cells but enhanced presentation of exogenous peptide to Type B T cells. Exposure to S. Typhimurium was sufficient to enhance Type B T-cell activation. Salmonella Typhimurium infection reduced surface expression of MHC-II, by an invariant chain-independent trafficking mechanism, resulting in accumulation of MHC-II in multi-vesicular bodies. Reduced MHC-II surface expression in S. Typhimurium-infected BMDCs correlated with reduced antigen presentation to Type A T cells. Salmonella infection is implicated in reactive arthritis. Therefore, polarisation of antigen presentation towards a Type B response by Salmonella may be a predisposing factor in autoimmune conditions such as reactive arthritis.
当抗原在不同的细胞内隔室中加载时，会产生被 A 型和 B 型 CD4(+) T 细胞亚群识别的独特肽-MHC-II 复合物。传统的 A 型 T 细胞无论加工途径如何，均可识别其肽表位，而非传统的 B 型 T 细胞仅识别外源提供的肽。B 型 T 细胞与自身免疫疾病有关，并可能通过逃避阴性选择而破坏自身耐受。在这里，我们表明沙门氏菌对 A 型和 B 型 T 细胞的抗原呈递有不同的影响。用沙门氏菌血清型 Typhimurium（S. Typhimurium）感染骨髓来源的树突状细胞（BMDC）可减少抗原呈递给 A 型 T 细胞，但增强外源肽呈递给 B 型 T 细胞。暴露于 S. Typhimurium 足以增强 B 型 T 细胞的激活。沙门氏菌 Typhimurium 通过非不变链依赖的运输机制降低 MHC-II 的表面表达，导致 MHC-II 在多泡体中积累。S. Typhimurium 感染的 BMDC 中 MHC-II 表面表达的降低与 A 型 T 细胞中抗原呈递的减少相关。沙门氏菌感染与反应性关节炎有关。因此，沙门氏菌将抗原呈递向 B 型反应的极化可能是反应性关节炎等自身免疫疾病的一个易感因素。
