Identification of a putative motif for binding of peptides to HLA-DQ2
Identification of a putative motif for binding of peptides to HLA-DQ2
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DOI：
10.1093/intimm/8.2.177
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发表时间：
1996-02-01
影响因子：
4.4
通讯作者：
Sollid, LM
中科院分区：
文献类型：
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作者：
Johansen, BH;Vartdal, F;Sollid, LM
为了理解决定肽与乳糜泻和1型糖尿病相关的HLA-DQ 2分子结合的规则，我们详细研究了肽OVA 258- 276 Y（IINFEKLTEWTSSNVMEERY）与DQ 2的强结合。首先，我们测试了一组N-和C-末端截短的变体，并发现核心结合区包含残基267- 276 Y。OVA 267- 276 Y肽的单丙氨酸取代分析显示，V-272、E（275）和C-末端Y的取代具有负效应，而N-271的取代具有正效应。具有V-272、E（275）和C-末端Y的OVA 267- 276 Y肽的聚丙氨酸类似物至少与原始肽结合得一样好。具有R（276）缺失的变体肽显示出降低的结合，表明该类似物中的锚残基在框外。为了进一步表征在OVA 267- 276 Y肽与DQ 2的结合中起作用的残基，我们测试了具有V-272、E（275）和C-末端Y残基取代的几种类似物的结合。我们的结果表明，结合DQ 2的肽在相对位置4、7和9（P4、P7和P9）具有锚残基。在P4和P7中优选具有带负电荷的或疏水性脂族但不带正电荷的侧链的残基，而在P9中优选具有庞大疏水性侧链的残基。
To understand the rules determining peptide binding to the celiac disease and type 1 diabetes mellitus associated HLA-DQ2 molecule, we have studied in detail the binding of a peptide OVA 258-276Y (IINFEKLTEWTSSNVMEERY) which exhibits strong binding to DQ2. First we tested a set of N- and C-terminal truncated variants, and found the core binding region to comprise residues 267-276Y. Single alanine substitution analysis of the OVA 267-276Y peptide revealed that replacements of V-272, E(275) and the C-terminal Y had negative effects whereas the substitution of N-271 had a positive effect. A polyalanine analogue of the OVA 267-276Y peptide with V-272, E(275) and a C-terminal Y bound at least as well as the original peptide. A variant peptide with a deletion of R(276) displayed decreased binding, suggesting that the anchor residues were out of frame in this analogue. To further characterize the residues playing a role in the binding of the OVA 267-276Y peptide to DQ2 we tested the binding of several analogues with substitutions for V-272, E(275) and the C-terminal Y residue. Our results indicate that peptides binding to DQ2 have anchor residues in relative positions 4, 7 and 9 (P4, P7 and P9). Residues with negatively charged or hydrophobic aliphatic but not positively charged side chains are preferred in P4 and P7, whereas residues with bulky hydrophobic side chains are preferred in P9.