Institute of Protein Biochemistry-CNR, Via Pietro Castellino 111, 80131, Naples, Italy.
Institute of Genetics and Biophysics-CNR, Via Pietro Castellino 111, 80131, Naples, Italy.
J Autoimmun. 2018 May;89:1-10. doi: 10.1016/j.jaut.2017.12.016. Epub 2018 Jan 10.
To date, the study of the impact of major hystocompatibility complex on autoimmunity has been prevalently focused on structural diversity of MHC molecules in binding and presentation of (auto)antigens to cognate T cells. Recently, a number of experimental evidences suggested new points of view to investigate the complex relationships between MHC gene expression and the individual predisposition to autoimmune diseases. Irrespective of the nature of the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as a threshold of T cell receptors engaged is required, for the activation and proliferation of autoantigen-reactive T cells. Moreover, it is well known that increased expression of MHC class II molecules may alter the T cell receptor repertoire during thymic development, and affect the survival and expansion of mature T cells. Many evidences confirmed that the level of both transcriptional and post-transcriptional regulation are involved in the modulation of the expression of MHC class II genes and that both contribute to the predisposition to autoimmune diseases. Here, we aim to focus some of these regulative aspects to better clarify the role of MHC class II genes in predisposition and development of autoimmunity.
迄今为止，对主要组织相容性复合体（major histocompatibility complex，MHC）对自身免疫影响的研究主要集中在 MHC 分子在结合和呈递（自身）抗原与同源 T 细胞方面的结构多样性。最近，大量实验证据提出了新的观点，以研究 MHC 基因表达与个体易患自身免疫性疾病之间的复杂关系。无论抗原的性质如何，自身抗原反应性 T 细胞的激活和增殖都需要达到 MHC-肽复合物的阈值，以及需要参与的 T 细胞受体的阈值。此外，众所周知，MHC Ⅱ类分子的表达增加可能会在胸腺发育过程中改变 T 细胞受体库，并影响成熟 T 细胞的存活和扩增。许多证据证实，转录和转录后调控的水平都参与了 MHC Ⅱ类基因表达的调节，并且都有助于自身免疫性疾病的易感性。在这里，我们旨在关注其中的一些调节方面，以更好地阐明 MHC Ⅱ类基因在自身免疫易感性和发展中的作用。
