TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide
TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide
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DOI：
10.1016/s0960-9822(98)70014-4
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发表时间：
1998-01-01
期刊：
影响因子：
9.2
通讯作者：
McMichael, AJ
中科院分区：
文献类型：
--
作者：
Braud, VM;Allan, DSJ;McMichael, AJ
背景资料：人类主要组织相容性复合体（MHC）Ib类分子HLA-E在大多数组织中转录，但对其在细胞内的定位知之甚少。我们最近表明，HLA-E结合信号序列衍生的肽从人MHC玻璃I分子ir：vitro.Results：使用一种新的表征抗体识别HLA-E，我们表明，HLA-E是在细胞表面表达，我们证明，HLA-E表面表达与MHC I类分子的存在，提供合适的前导序列肽能够结合到HLA-E。对HLA-E与内质网中分子相互作用的进一步研究表明，HLA-E与抗原加工相关转运蛋白（TAP）和钙网蛋白相关，并且HLA-E的表达是TAP依赖性和Tapasin依赖性的。此外，HLA-E解离TAP后，结合的MHC I类前导序列peptides.Conclusion：这些实验建立了HLA-E的表面表达的调节由一个限制性池的肽从MHO I类分子的前导序列的结合。HLA-E与MHC Ⅰ类分子表面表达的相关性可能与HLA-E的功能有关。我们的研究结果还表明，虽然这些HLA-E结合肽来源于信号序列，但它们可能被释放回胞质溶胶中，随后被TAP复合物易位并加载到HLA-E分子上。
Background: The human major histocompatibility complex (MHC) class Ib molecule HLA-E is transcribed in most tissues but little is known about its localisation within the cell. We have recently shown that HLA-E binds signal-sequence-derived peptides from human MHC Glass I molecules ir: vitro.Results: Using a newly characterised antibody recognising HLA-E, we show that HLA-E is expressed at the cell surface, We demonstrate that HLA-E surface expression is correlated with the presence of MHC class I molecules which provide suitable leader sequence peptides capable of binding to HLA-E. Further studies on the interaction of HLA-E with molecules in the endoplasmic reticulum revealed that HLA-E associates with the transporter associated with antigen processing (TAP) and calreticulin, and that HLA-E expression is TAP-dependent and tapasin-dependent. In addition, HLA-E dissociates from TAP upon binding of MHC class I leader sequence peptides.Conclusion: These experiments establish that surface expression of HLA-E is regulated by the binding of a restricted pool of peptides from the leader sequence of MHO class I molecules. The correlation between HLA-E and MHC class I surface expression might be relevant to the function of HLA-E. Our results also show that, although these HLA-E binding peptides are derived from signal sequences, they may be released back into the cytosol and subsequently translocated by the TAP complex and loaded onto HLA-E molecules.