Bjørnestad Synne Arstad, Solbakken Monica Hongrø, Jakobsen Kjetill S, Jentoft Sissel, Bakke Oddmund, Progida Cinzia
Section of Physiology and Cell Biology, Department of Biosciences, University of Oslo, Oslo, Norway.
Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences, University of Oslo, Oslo, Norway.
Front Cell Dev Biol. 2023 Jan 25;11:1050323. doi: 10.3389/fcell.2023.1050323. eCollection 2023.
Major histocompatibility complex (MHC) class I and II are crucial for the adaptive immune system because they are involved in peptide presentation to T cells. Until recently, it was believed that MHC genes and their associated immune components had been conserved since their evolutionary emergence in jawed fish. However, sequencing of the Atlantic cod () genome revealed a loss of MHC class II genes, and an extreme expansion of MHC class I genes. These findings lead to the hypothesis that a loss of the MHC class II pathway coincided with a more versatile use of MHC class I, but so far there is no direct experimental evidence in support of this. To gain a deeper understanding of the function of the expanded MHC class I, we selected five MHC class I gene variants representing five of the six clades identified in previous studies and investigated their intracellular localization in human and Atlantic cod larval cells. Intriguingly, we uncovered that all selected MHC class I variants localize to endolysosomal compartments in Atlantic cod cells. Additionally, by introducing point mutations or deletions in the cytosolic tail, we found that hypothetical sorting signals in the MHC class I cytosolic tail do not influence MHC class I trafficking. Moreover, we demonstrated that in Atlantic cod, tapasin and MHC class I colocalize on endolysosomes suggesting that peptide-loading assistance and stabilization of MHC class I occurs outside the endoplasmic reticulum. Altogether, our results demonstrate that MHC class I from Atlantic cod is sorted to the endolysosomal system, which may indicate that it interacts with exogenous peptides for potential cross presentation.
主要组织相容性复合体（MHC）I类和II类对于适应性免疫系统至关重要，因为它们参与向T细胞呈递肽段。直到最近，人们一直认为MHC基因及其相关的免疫成分自其在有颌鱼类中进化出现以来一直保守。然而，大西洋鳕鱼（）基因组测序显示MHC II类基因缺失，而MHC I类基因极度扩增。这些发现导致了这样一种假设，即MHC II类途径的缺失与MHC I类更广泛的用途同时发生，但迄今为止尚无直接的实验证据支持这一点。为了更深入地了解扩增的MHC I类的功能，我们选择了代表先前研究中鉴定的六个分支中的五个的五个MHC I类基因变体，并研究了它们在人类和大西洋鳕鱼幼虫细胞中的细胞内定位。有趣的是，我们发现所有选定的MHC I类变体都定位于大西洋鳕鱼细胞中的内溶酶体区室。此外，通过在胞质尾部引入点突变或缺失，我们发现MHC I类胞质尾部中的假设分选信号不影响MHC I类的运输。此外，我们证明在大西洋鳕鱼中，塔帕辛和MHC I类在内溶酶体上共定位，这表明MHC I类的肽负载辅助和稳定作用发生在内质网之外。总之，我们的结果表明，来自大西洋鳕鱼的MHC I类被分选到内溶酶体系统，这可能表明它与外源性肽相互作用以进行潜在的交叉呈递。
