Gaston J S, Goodall J C, Young J L, Young S P
Department of Medicine, University of Cambridge, United Kingdom.
Hum Immunol. 1997 Apr 15;54(1):40-7. doi: 10.1016/s0198-8859(97)00003-7.
Human T-cell clones that recognize a peptide from mycobacterial heat shock protein 60 in the context of HLA-DP were found to be sensitive to changes in the DPA1 chain of the restricting element, optimal responses being seen with the combination HLA-DPA10201 and HLA-DPB0301. HLA-DP dimers containing HLA-DPA1*01 were only able to present antigenic peptides to T-cell clones when peptides were present throughout the period of coculture of T cells with antigen presenting cells. In contrast the optimal HLA-DP dimer could also stimulate T-cell clones maximally when incubated with peptides for 1 h and then thoroughly washed. This suggests that the DPA1 polymorphism influenced the strength of binding of antigenic peptides to the HLA-DP dimer. Modeling studies identified amino acid 31 of DPA1 as the polymorphic residue most likely to account for this effect. This is the first demonstration that the relatively limited polymorphism displayed by DPA1 has functional consequences.
已发现，在HLA - DP背景下识别来自分枝杆菌热休克蛋白60的肽段的人T细胞克隆，对限制元件的DPA1链变化敏感，最佳反应见于HLA - DPA10201和HLA - DPB0301组合。含有HLA - DPA1*01的HLA - DP二聚体，只有在T细胞与抗原呈递细胞共培养期间全程存在肽段时，才能将抗原肽呈递给T细胞克隆。相比之下，最佳的HLA - DP二聚体在与肽段孵育1小时然后彻底洗涤后，也能最大程度地刺激T细胞克隆。这表明DPA1多态性影响抗原肽与HLA - DP二聚体的结合强度。建模研究确定DPA1的第31位氨基酸是最有可能导致这种效应的多态性残基。这是首次证明DPA1所显示的相对有限的多态性具有功能后果。
