Karamooz Elham, Peterson Jessie, Tammen Allison, Soma Shogo, Kim Se-Jin, Lewinsohn David
Portland VA Medical Center.
Oregon Health & Science University.
Res Sq. 2023 Aug 30:rs.3.rs-3154465. doi: 10.21203/rs.3.rs-3154465/v1.
MR1 is a ubiquitously expressed MHC-Ib molecule that presents microbial metabolites to MR1-restricted T cells, but there are differences in the antigen presentation pathway of an intracellular microbe compared to exogenous antigen. We have shown the importance of endosomal trafficking proteins in MR1-dependent presentation of (Mtb). Two pore channels (TPCs) are endosomal calcium channels that regulate endosomal trafficking. Due to their location on endosomes, we hypothesized that TPCs could be required for MR1-dependent presentation of antigens derived from the intracellular microbe Mtb. We found that TPCs are critical for the presentation of Mtb by MR1; inhibition of TPCs had no effect on MR1 presentation of extracellular (exogenous) antigens, HLA-B presentation, or HLA-II presentation. Finally, we found that the calcium sensitive trafficking protein Synaptotagmin 7 was also key in the presentation of Mtb by MR1. This calcium-dependent endosomal pathway is a novel mechanism by which the immune system can sample intracellular antigens.
MR1是一种广泛表达的MHC-Ib分子，它将微生物代谢产物呈递给受MR1限制的T细胞，但与外源性抗原相比，细胞内微生物的抗原呈递途径存在差异。我们已经证明了内体运输蛋白在依赖MR1的结核分枝杆菌呈递中的重要性。双孔通道（TPCs）是调节内体运输的内体钙通道。由于它们在内体上的位置，我们推测TPCs可能是依赖MR1呈递来自细胞内微生物结核分枝杆菌的抗原所必需的。我们发现TPCs对于MR1呈递结核分枝杆菌至关重要；抑制TPCs对MR1呈递细胞外（外源性）抗原、HLA-B呈递或HLA-II呈递没有影响。最后，我们发现钙敏感运输蛋白突触结合蛋白7在MR1呈递结核分枝杆菌中也起着关键作用。这种依赖钙的内体途径是免疫系统能够采样细胞内抗原的一种新机制。
