HLA-B27 polymorphism at position 116 critically influences the association with TAP/tapasin, intracellular trafficking and conformational homodimers formation
HLA-B27 polymorphism at position 116 critically influences the association with TAP/tapasin, intracellular trafficking and conformational homodimers formation
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DOI：
10.1016/j.molimm.2008.11.023
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发表时间：
2009-04-01
影响因子：
3.6
通讯作者：
Lopez-Larrea, C.
中科院分区：
文献类型：
--
作者：
Blanco-Gelaz, M. A.;Suarez-Alvareza, B.;Lopez-Larrea, C.
HLA-B27赋予强直性脊柱炎的易感性，但AS的发病机制尚不清楚。我们确定了多态性和tapasin依赖性对HLA-B27亚型表达、细胞内成熟和同源二聚体形成的影响。我们发现，在116位具有组氨酸的B*2709与抗原加工复合物相关的转运蛋白密切相关，与细胞表面上较低的非构象表达、延迟的成熟率和最小的构象和非构象同二聚体形成相关。相反，B*2705显示出对与抗原加工相关转运蛋白的低依赖性、更快的细胞内成熟和增加的同二聚体形式的水平。Tapasin的缺乏显著影响了B*2709的细胞内成熟速率，显示出更快的转运出内质网，但与B*2705相似。所有检查的B27亚型在没有tapasin的情况下都不能表达构象同源二聚体形式。这项研究表明，HLA-B27多态性驱动tapasin依赖性，细胞内成熟率和同源二聚体的表达。(C)2009年由Elsevier Ltd.出版
HLA-B27 confers susceptibility to ankylosing spondylitis but AS disease mechanisms remain unknown. We determined here the effect of polymorphism and tapasin dependence on the expression, intracellular maturation and homodimer formation among HLA-B27 subtypes. We found that B*2709 with a histidine at position 116 was strongly associated with the transporter associated with antigen processing complex, correlated with lower, non-conformational expression on the cell surface, delayed maturation rate and minimal conformational and non-conformational homodimer formation. in contrast, B*2705 showed a low dependence for transporter associated with antigen processing, faster intracellular maturation and increased levels of homodimeric forms. The absence of tapasin significantly influenced the rate of intracellular maturation of B*2709, showing faster transport out of the endoplasmic reticulum, but similar to that of B*2705. All B27 subtypes examined were unable to express conformational homodimeric forms in the absence of tapasin. This study suggests that HLA-B27 polymorphism drives the tapasin dependency, rates of intracellular maturation and expressions of homodimers. (C) 2009 Published by Elsevier Ltd.