Complexes of two cohorts of CLIP peptides and HLA-DQ2 of the autoimmune DR3-DQ2 haplotype are poor substrates for HLA-DM.

Complexes of two cohorts of CLIP peptides and HLA-DQ2 of the autoimmune DR3-DQ2 haplotype are poor substrates for HLA-DM.
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DOI:
10.4049/jimmunol.181.8.5451
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发表时间:
2008-10-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Sollid LM
Sollid LM
中科院分区:
其他
文献类型:
--
作者:
Fallang LE;Roh S;Holm A;Bergseng E;Yoon T;Fleckenstein B;Bandyopadhyay A;Mellins ED;Sollid LM

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非典型不变链(Ii)3 CLIP片段(CLIP2)被发现与从细胞裂解物中纯化的HLA-DQ2 (DQ2)相关。我们将CLIP2 (Ii 96-104)的结合位点定位到DQ2,发现脯氨酸位于P1位置,而与此相反,CLIP1 (Ii 83-101)的结合位点在P1位置有蛋氨酸。CLIP1/2肽是主要的肽种,甚至对于来自HLA-DM (DM)表达细胞的DQ2也是如此。我们假设DQ2- clip1 /2可能是DM的不良底物。我们测量了DM介导的高亲和力指示肽的CLIP肽交换,发现与HLA-DR3 (DR3)相比,DQ2的效率较低。与DQ1相比,DQ2的DM-DQ结合和DM伴侣对DQ构象和水平的影响也有所降低。我们认为,DQ2与Ii和DM的不寻常相互作用可能为DQ2已知的疾病关联提供了基础。
Atypical invariant chain (Ii)3 CLIP fragments (CLIP2) have been found in association with HLA-DQ2 (DQ2) purified from cell lysates. We mapped the binding register of CLIP2 (Ii 96-104) to DQ2 and found proline at the P1 position, in contrast to the canonical CLIP1 (Ii 83-101) register with methionine at P1. CLIP1/2 peptides are the predominant peptide species, even for DQ2 from HLA-DM (DM)-expressing cells. We hypothesized that DQ2-CLIP1/2 might be poor substrates for DM. We measured DM-mediated exchange of CLIP peptides for high affinity indicator peptides and found it is inefficient for DQ2 compared to HLA-DR3 (DR3). DM-DQ binding and DM chaperone effects on conformation and levels of DQ are also reduced for DQ2, compared to DQ1. We suggest that the unusual interaction of DQ2 with Ii and DM may provide a basis for the known disease associations of DQ2.
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