Smyth Lesley Ann, Harker Nicola, Turnbull Wayne, El-Doueik Haytham, Klavinskis Linda, Kioussis Dimitris, Lombardi Giovanna, Lechler Robert
Department of Nephrology and Transplantation, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom.
J Immunol. 2008 Sep 1;181(5):3212-20. doi: 10.4049/jimmunol.181.5.3212.
Intercellular exchange of MHC molecules has been reported between many cells, including professional and nonprofessional APCs. This phenomenon may contribute to T cell immunity to pathogens. In this study, we addressed whether the transfer of MHC class I:peptide complexes between cells plays a role in T cell responses and compare this to conventional cross-presentation. We observed that dsRNA-matured bone marrow-derived dendritic cells (BMDCs) acquired peptide:MHC complexes from other BMDCs either pulsed with OVA(257-264) peptide, soluble OVA, or infected with a recombinant adenovirus expressing OVA. In addition, BMDCs were capable of acquiring MHC:peptide complexes from epithelial cells. Spleen-derived CD8alpha(+) and CD8alpha(-) dendritic cells (DCs) also acquired MHC:peptide complexes from BMDCs pulsed with OVA(257-264) peptide. However, the efficiency of acquisition by these ex vivo derived DCs is much lower than acquisition by BMDC. In all cases, the acquired MHC:peptide complexes were functional in that they induced Ag-specific CD8(+) T cell proliferation. The efficiency of MHC transfer was compared with cross-presentation for splenic CD8alpha(+) and CD8alpha(-) as well as BMDCs. CD8alpha(+) DCs were more efficient at inducing T cell proliferation when they acquired Ag via cross-presentation, the opposite was observed for BMDCs and splenic CD8alpha(-) DCs. We conclude from these observations that the relative efficiency of MHC transfer vs cross-presentation differs markedly between different DC subsets.
据报道，包括专职和非专职抗原呈递细胞（APC）在内的许多细胞之间存在主要组织相容性复合体（MHC）分子的细胞间交换。这种现象可能有助于T细胞对病原体的免疫。在本研究中，我们探讨了细胞间MHC I类：肽复合物的转移是否在T细胞反应中起作用，并将其与传统的交叉呈递进行比较。我们观察到，双链RNA成熟的骨髓来源树突状细胞（BMDC）从其他BMDC获得肽：MHC复合物，这些BMDC要么用OVA（257-264）肽脉冲处理、可溶性OVA处理，要么感染表达OVA的重组腺病毒。此外，BMDC能够从上皮细胞获得MHC：肽复合物。脾脏来源的CD8α（+）和CD8α（-）树突状细胞（DC）也从用OVA（257-264）肽脉冲处理的BMDC获得MHC：肽复合物。然而，这些体外来源的DC的获取效率远低于BMDC的获取效率。在所有情况下，获得的MHC：肽复合物都具有功能，因为它们诱导了抗原特异性CD8（+）T细胞增殖。将MHC转移效率与脾脏CD8α（+）和CD8α（-）以及BMDC的交叉呈递效率进行了比较。当CD8α（+）DC通过交叉呈递获得抗原时，它们在诱导T细胞增殖方面更有效，而BMDC和脾脏CD8α（-）DC则观察到相反的情况。我们从这些观察结果得出结论，不同DC亚群之间MHC转移与交叉呈递的相对效率存在显著差异。
