The love and hate relationship of HLA-DM/DO in the selection of immunodominant epitopes.
The love and hate relationship of HLA-DM/DO in the selection of immunodominant epitopes.
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DOI：
10.1016/j.coi.2020.05.007
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发表时间：
2020-06
影响因子：
7
通讯作者：
Sadegh-Nasseri S
中科院分区：
文献类型：
--
作者：
Welsh RA;Sadegh-Nasseri S
CD 4 T细胞的成功活化以抗原呈递细胞成功加工、从外源抗原中选择II类免疫显性表位并将其呈递给同源T细胞的能力为中心。为了实现这一点，新合成的MHC-II分子被转移到一个专门的隔室，其中含有外源性抗原和II类加工机器。在这里，在称为“编辑”的过程中，II类辅助分子DM（人HLA-DM;鼠H2-M）促进外源肽加载和选择至MHC II类分子，从而确保免疫显性表位的适当选择。主要存在于B细胞和胸腺上皮中的第二种II类辅助分子DO（人HLA-DO;鼠H2-O）也有助于免疫显性表位的选择。然而，尽管对DM如何起作用有大量的机械见解，但理解DO对表位选择的贡献已被证明是非常具有挑战性的。在这篇综述中，我们试图讨论在过去三年中发表的体外和体内数据与DO的生物学的见解。
Successful activation of CD4 T cells is centered around the ability of antigen presenting cells to successfully process, select Class II immunodominant epitopes from exogenous antigens and to present it to cognate T cells. To achieve this, newly synthesized MHC-II molecules are transferred to a specialized compartment which contain both exogenous antigens and the Class II processing machinery. Here in a process known as ‘editing,’ the Class II accessory molecule DM (HLA-DM human; murine H2-M) facilitates the loading and selection of exogenous peptides to MHC class II molecules thereby assuring proper selection of immunodominant epitopes. A second Class II accessory molecule, DO (HLA-DO human; murine H2-O), mainly present in B cells and thymic epithelium also contributes to the selection of immunodominant epitopes. Yet, despite a wealth of mechanistic insights into how DM functions, understanding the contributions of DO to epitope selection has proven to be highly challenging. In this review, we have attempted to discuss published in vitro and in vivo data during the past three years with insights into the biology of DO.
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