The nonclassical MHC class I molecule Qa-1 forms unstable peptide complexes
The nonclassical MHC class I molecule Qa-1 forms unstable peptide complexes
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DOI：
10.4049/jimmunol.172.3.1661
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Jensen, PE
中科院分区：
文献类型：
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作者：
Kambayashi, T;Kraft-Leavy, JR;Jensen, PE
MHC类Ib分子Qa-1是小鼠CD94/NKG2A抑制受体在NK细胞上表达的主要配体，除了将Ags呈递给T细胞亚群。CD94/NKG2A受体特异性识别与MHC la类先导序列衍生肽Qdm结合的Qa-1。生理条件下，Qdm是装载在Qa-1上的优势肽，该肽具有与Qa-1结合的最佳序列。肽解离实验表明，在37℃的温度下，Qdm与可溶性或细胞表面的Qa-1(b)分子解离时间为1.5小时。相比之下，与MHC类la分子h - 2k (b)结合的最佳肽（SIINFEKL）复合物与t（1/2）在11至31小时的范围内解离。与K-b相比，细胞表面Qa-1(b)分子的稳定性与结合的肽无关，并且一些观察表明，空细胞表面Qa-1(b)分子可能异常稳定。与Qdm与Qa-1(b)的快速解离速率一致，在细胞表面不能连续生成新的Qa-1(b)/Qdm复合物的条件下，细胞容易被CD94/NKG2A(+) NK细胞裂解。这些结果支持了Qa-1被选择为无法形成高度稳定肽复合物的特化MHC分子的假设。我们认为CD94/NKG2A-Qa-1/Qdm识别系统已经发展成为MHC I类生物合成和银呈递途径完整性的快速传感器。
The MHC class Ib molecule Qa-1 is the primary ligand for mouse CD94/NKG2A inhibitory receptors expressed on NK cells, in addition to presenting Ags to a subpopulation of T cells. CD94/NKG2A receptors specifically recognize Qa-1 bound to the MHC class la leader sequence-derived peptide Qdm. Qdm is the dominant peptide loaded onto Qa-1 under physiological conditions and this peptide has an optimal sequence for binding to Qa-1. Peptide dissociation experiments demonstrated that Qdm dissociates from soluble or cell surface Qa-1(b) molecules with a t(1/2) of similar to1.5 h at 37degreesC. In comparison, complexes of an optimal peptide (SIINFEKL) bound to the MHC class la molecule H-2K(b) dissociated with a t(1/2) in the range from 11 to 31 h. In contrast to K-b, the stability of cell surface Qa-1(b) molecules was independent of bound peptides, and several observations suggested that empty cell surface Qa-1(b) molecules might be unusually stable. Consistent with the rapid dissociation rate of Qdm from Qa-1(b), cells become susceptible to lysis by CD94/NKG2A(+) NK cells under conditions in which new Qa-1(b)/Qdm complexes cannot be continuously generated at the cell surface. These results support the hypothesis that Qa-1 has been selected as a specialized MHC molecule that is unable to form highly stable peptide complexes. We propose that the CD94/NKG2A-Qa-1/Qdm recognition system has evolved as a rapid sensor of the integrity of the MHC class I biosynthesis and Ag presentation pathway.