Zehn Dietmar, Cohen Cyril J, Reiter Yoram, Walden Peter
Department of Dermatology, Charité, University Medicine Berlin, Humboldt University, Schumannstrasse 20/21, D-10117 Berlin, Germany.
Int Immunol. 2006 Dec;18(12):1647-54. doi: 10.1093/intimm/dxl098. Epub 2006 Oct 11.
Dendritic cells (DCs) play a key role in the induction of cellular immune responses by harvesting antigens from peripheral tissue for cross-priming CD8(+) T cells. It has been demonstrated that apoptotic bodies, whole- or degraded-cell-associated or soluble antigens as well as heat shock protein-bound peptides can be taken up, processed and cross-presented by DCs. Since cells are continuously releasing peptides from their surface MHC molecules, DCs in the tissues are exposed to such peptides and might process and present them to T cells as an additional pathway for cross-priming. To investigate this possibility, we compared and characterized the presentation of exogenous peptides by DCs and other cell types employing novel recombinant antibodies with TCR-like specificities for specific peptide-MHC complexes (pMHCs). These analyses reveal that loading of immature and mature DCs with peptide is far less efficient than it is for monocytes, T and B lymphocytes, B-lymphoblastoid, melanoma and TAP-deficient T2 cells. This inefficiency of peptide transfer to the MHC molecules of DCs makes it unlikely that these cells recycle peptides released from the MHC molecules of other cells and may explain why cross-presentation of such peptides has not yet been observed.
树突状细胞(DCs)通过从外周组织摄取抗原以交叉启动CD8(+) T细胞,在细胞免疫反应的诱导中发挥关键作用。已经证明,凋亡小体、全细胞或降解细胞相关抗原以及热休克蛋白结合肽均可被DCs摄取、加工和交叉呈递。由于细胞不断从其表面MHC分子释放肽,组织中的DCs会接触到此类肽,并可能将其加工并呈递给T细胞,作为交叉启动的另一条途径。为了研究这种可能性,我们使用对特定肽-MHC复合物(pMHCs)具有TCR样特异性的新型重组抗体,比较并表征了DCs和其他细胞类型对外源肽的呈递情况。这些分析表明,用肽加载未成熟和成熟DCs的效率远低于单核细胞、T和B淋巴细胞、B淋巴母细胞、黑色素瘤细胞和TAP缺陷型T2细胞。肽转移到DCs的MHC分子的这种低效率使得这些细胞不太可能循环利用从其他细胞的MHC分子释放的肽,这也许可以解释为什么尚未观察到此类肽的交叉呈递。