Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Adv Exp Med Biol. 2024;1444:51-65. doi: 10.1007/978-981-99-9781-7_4.
Major histocompatibility complex (MHC) class II molecules play a crucial role in immunity by presenting peptide antigens to helper T cells. Immune cells are generally tolerant to self-antigens. However, when self-tolerance is broken, immune cells attack normal tissues or cells, leading to the development of autoimmune diseases. Genome-wide association studies have shown that MHC class II is the gene most strongly associated with the risk of most autoimmune diseases. When misfolded self-antigens, called neoself antigens, are associated with MHC class II molecules in the endoplasmic reticulum, they are transported by the MHC class II molecules to the cell surface without being processed into peptides. Moreover, neoself antigens that are complexed with MHC class II molecules of autoimmune disease risk alleles exhibit distinct antigenicities compared to normal self-antigens, making them the primary targets of autoantibodies in various autoimmune diseases. Elucidation of the immunological functions of neoself antigens presented on MHC class II molecules is crucial for understanding the mechanism of autoimmune diseases.
主要组织相容性复合体 (MHC) Ⅱ类分子通过将肽抗原呈递给辅助性 T 细胞在免疫中发挥关键作用。免疫细胞通常对自身抗原具有耐受性。然而，当自身耐受性被打破时，免疫细胞会攻击正常组织或细胞，导致自身免疫性疾病的发展。全基因组关联研究表明，MHC Ⅱ类是与大多数自身免疫性疾病风险相关性最强的基因。当错误折叠的自身抗原，称为新自身抗原，与内质网中的 MHC Ⅱ类分子结合时，它们会在未被加工成肽的情况下由 MHC Ⅱ类分子运输到细胞表面。此外，与自身免疫疾病风险等位基因的 MHC Ⅱ类分子结合的新自身抗原与正常自身抗原相比表现出不同的抗原性，使它们成为各种自身免疫性疾病中自身抗体的主要靶标。阐明 MHC Ⅱ类分子呈递的新自身抗原的免疫学功能对于理解自身免疫性疾病的机制至关重要。
