自身免疫性DR3-DQ2单倍型的两组CLIP肽与HLA-DQ2的复合物是HLA-DM的不良底物。
Complexes of two cohorts of CLIP peptides and HLA-DQ2 of the autoimmune DR3-DQ2 haplotype are poor substrates for HLA-DM.
作者信息
Fallang Lars-Egil, Roh Sujin, Holm Anders, Bergseng Elin, Yoon Taejin, Fleckenstein Burkhard, Bandyopadhyay Arunima, Mellins Elizabeth D, Sollid Ludvig M
机构信息
Centre for Immune Regulation and Institute of Immunology, University of Oslo, Rikshospitalet, N-0027 Oslo, Norway.
Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
出版信息
J Immunol. 2008 Oct 15;181(8):5451-5461. doi: 10.4049/jimmunol.181.8.5451.
Abstract
Atypical invariant chain (Ii) 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 and other peptides for high-affinity indicator peptides and found it is inefficient for DQ2. DM-DQ-binding and DM chaperone effects on conformation and levels of DQ are also reduced for DQ2, compared with DQ1. We suggest that the unusual interaction of DQ2 with Ii and DM may provide a basis for the known disease associations of DQ2.
摘要
在从细胞裂解物中纯化的HLA-DQ2（DQ2）中发现了非典型恒定链（Ii）CLIP片段（CLIP2）。我们将CLIP2（Ii 96-104）与DQ2的结合位点进行了定位，发现P1位置为脯氨酸，这与P1位置为甲硫氨酸的典型CLIP1（Ii 83-101）位点不同。CLIP1/2肽是主要的肽种类，即使对于来自表达HLA-DM（DM）的细胞的DQ2也是如此。我们推测DQ2-CLIP1/2可能是DM的不良底物。我们测量了DM介导的CLIP和其他肽与高亲和力指示肽的交换，发现其对DQ2效率低下。与DQ1相比，DQ2的DM-DQ结合以及DM对DQ构象和水平的伴侣作用也降低了。我们认为DQ2与Ii和DM的异常相互作用可能为DQ2已知的疾病关联提供基础。
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本文引用的文献
1
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Nat Immunol. 2007 Jan;8(1):92-100. doi: 10.1038/ni1414. Epub 2006 Dec 3.
2
Amino-terminal flanking residues determine the conformation of a peptide-class II MHC complex.氨基末端侧翼残基决定了肽 - Ⅱ类主要组织相容性复合体的构象。
J Immunol. 2006 Mar 1;176(5):2958-68. doi: 10.4049/jimmunol.176.5.2958.
3
DM peptide-editing function leads to immunodominance in CD4 T cell responses in vivo.DM肽编辑功能在体内CD4 T细胞应答中导致免疫显性。
J Immunol. 2005 Nov 15;175(10):6473-80. doi: 10.4049/jimmunol.175.10.6473.
4
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5
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J Biol Chem. 2005 Jun 10;280(23):21791-6. doi: 10.1074/jbc.M501558200. Epub 2005 Apr 12.
6
Ectopic expression of HLA-DO in mouse dendritic cells diminishes MHC class II antigen presentation.HLA-DO在小鼠树突状细胞中的异位表达会减少MHC II类抗原呈递。
J Immunol. 2004 Aug 1;173(3):1549-60. doi: 10.4049/jimmunol.173.3.1549.
7
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8
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Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4175-9. doi: 10.1073/pnas.0306885101. Epub 2004 Mar 12.
9
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J Immunol. 2004 Jan 15;172(2):1109-17. doi: 10.4049/jimmunol.172.2.1109.
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