Chung Shanzou, Knox-Johnson Isambard G, Gazzard Sarah E, Song Runqiu, Le Ngoc H, Cullen-McEwen Luise A, Bertram John F, Purcell Anthony W, Braun Asolina
Department of Biochemistry and Molecular Biology, Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Clayton, VIC 3800, Australia.
Methods Protoc. 2025 Apr 24;8(3):43. doi: 10.3390/mps8030043.
Antigen presentation on major histocompatibility complex (MHC) molecules is central to the initiation of immune responses, and a lot of our understanding about the antigen processing and presentation pathway has been gained through studies in mice. MHC molecules are the most genetically diverse genes; consequently, mouse strains differ substantially in their MHC make up and resulting antigen presentation. Swiss mice are commonly used in pharmacological research, yet our understanding of antigen presentation in this strain is surprisingly limited. Here, we have tested a range of anti-MHC antibodies and present a range of clones suitable to analyse MHC class I and class II molecules in Swiss mice who have the H2-q MHC haplotype. Moreover, we demonstrate using immunopeptidomics that clones 28-12-8, 34-1-2, MKD6, and N22 are also suited to isolate MHC class I and class II ligands in this mouse strain. Thus, this work also establishes a first experimental account of the H2-q-derived thymus and spleen immunopeptidome in Swiss mice which bears strong resemblance with ligands isolated from the H2-d MHC haplotype of Balb/C mice. The analysis of source proteins shows common but also organ- and function-specific antigen presentation in line with the involvement of the thymus in tolerance induction and the function of the spleen as a site of immune responses.
主要组织相容性复合体（MHC）分子上的抗原呈递是免疫反应启动的核心，我们对抗原加工和呈递途径的许多理解都来自于对小鼠的研究。MHC分子是遗传多样性最高的基因；因此，不同品系小鼠的MHC组成和由此产生的抗原呈递存在很大差异。瑞士小鼠常用于药理学研究，但我们对该品系抗原呈递的了解却出奇地有限。在此，我们测试了一系列抗MHC抗体，并展示了一系列适合分析具有H2-q MHC单倍型的瑞士小鼠中MHC I类和II类分子的克隆。此外，我们通过免疫肽组学证明，克隆28-12-8、34-1-2、MKD6和N22也适用于分离该小鼠品系中的MHC I类和II类配体。因此，这项工作还首次建立了瑞士小鼠中源自H2-q的胸腺和脾脏免疫肽组的实验记录，该记录与从Balb/C小鼠的H2-d MHC单倍型中分离出的配体有很强的相似性。对来源蛋白的分析显示了共同的，但也有器官和功能特异性的抗原呈递，这与胸腺在耐受性诱导中的作用以及脾脏作为免疫反应场所的功能一致。
