PDF(Pubmed)
Abstract：
In B cells, antigen processing and peptide-antigen (pAg) presentation is essential to ignite high-affinity antibody responses with the help of cognate T cells. B cells efficiently internalize and direct specific antigens for processing and loading onto MHCII. This critical step, which enables pAg presentation, occurs in MHCII compartments (MIICs) which possess the enzymatic machinery for pAg loading on MHCII. The intracellular transport systems that guide antigen and maintain this unique compartment remain enigmatic. Here, we probed the possible functional role of two known endosomal proteins, the Rab family small GTPases Rab7 and Rab9, that are both reported to colocalize with internalized antigen. As compared to Rab9, we found Rab7 to exhibit a higher overlap with antigen and MIIC components. Rab7 also showed a higher association with antigen degradation. The inhibition of Rab7 drastically decreased pAg presentation. Additionally, we detected the strong colocalization of perinuclearly clustered and presumably MIIC-associated antigen with autophagy protein LC3. When we pharmacologically inhibited autophagy, pAg presentation was inhibited. Together, our data promote Rab7 as an important regulator of antigen processing and, considering the previously reported functions of Rab7 in autophagy, this also raises the possibility of the involvement of autophagy-related machinery in this process.
摘要：
在B细胞中，抗原加工和肽抗原（pAg）呈递对于在同源T细胞的帮助下点燃高亲和力抗体应答至关重要。B细胞有效地内化和引导特异性抗原以用于加工和装载到MHCII上。这关键的一步,这使得pAg呈现，发生在MHCII隔室（MIIC）中，该隔室具有将pAg负载在MHCII上的酶机制。引导抗原并维持这种独特区室的细胞内转运系统仍然是神秘的。这里,我们探讨了两种已知的内体蛋白可能的功能作用，Rab家族小GTP酶Rab7和Rab9，据报道两者都与内化抗原共定位。与Rab9相比,我们发现Rab7与抗原和MIIC组分表现出更高的重叠。Rab7还显示与抗原降解的较高相关性。Rab7的抑制显著降低了pAg的呈现。此外,我们检测到核周聚集和推测MIIC相关抗原与自噬蛋白LC3的强共定位。当我们在药理学上抑制自噬时，pAg表达被抑制。一起,我们的数据推动Rab7成为抗原加工的重要调节剂，考虑到先前报道的Rab7在自噬中的功能，这也增加了自噬相关机制参与这一过程的可能性.
