Manickasingham S, Reis e Sousa C
Immunobiology Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
J Immunol. 2000 Nov 1;165(9):5027-34. doi: 10.4049/jimmunol.165.9.5027.
B cells and dendritic cells (DC) internalize and degrade exogenous Ags and present them as peptides bound to MHC class II molecules for scrutiny by CD4(+) T cells. Here we use an Ab specific for a processed form of the model Ag, hen egg lysozyme (HEL), to demonstrate that this protein is not efficiently presented by lymph node DC following s.c. immunization. HEL presentation by the DC can be dramatically enhanced upon coinjection of a microbial adjuvant, which appears to act by enhancing peptide loading onto MHC class II. CD40 cross-linking or the presence of a high frequency of T cells specific for HEL can similarly improve presentation by DC in vivo. For any of these activating stimuli, CD8alpha(+) DC consistently display the highest proportion of HEL-loaded MHC class II molecules. These data indicate that exogenous Ags can be displayed to T cells in lymphoid tissues by a large cohort of resident DC whose presentation is regulated by innate and adaptive stimuli. Our data further reveal the existence of a feedback mechanism that augments Ag presentation during cognate APC-T cell interactions.
B细胞和树突状细胞（DC）内化并降解外源性抗原，并将其作为与II类主要组织相容性复合体（MHC）分子结合的肽段呈递，以供CD4(+) T细胞检查。在此，我们使用一种针对模型抗原——鸡卵溶菌酶（HEL）的加工形式的抗体，来证明在皮下免疫后，这种蛋白质不能被淋巴结DC有效地呈递。在共注射微生物佐剂后，DC对HEL的呈递可显著增强，这似乎是通过增强肽段加载到II类MHC分子上起作用的。CD40交联或存在针对HEL的高频T细胞同样可以在体内改善DC的呈递。对于这些激活刺激中的任何一种，CD8α(+) DC始终显示出加载有HEL的II类MHC分子的最高比例。这些数据表明，外源性抗原可由大量驻留DC在淋巴组织中呈递给T细胞，其呈递受固有和适应性刺激的调节。我们的数据进一步揭示了一种反馈机制的存在，该机制在同源抗原呈递细胞-T细胞相互作用期间增强抗原呈递。
