Dominance of the BV17 element in nickel-specific human T cell receptors relates to severity of contact sensitivity
Dominance of the BV17 element in nickel-specific human T cell receptors relates to severity of contact sensitivity
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DOI：
10.1002/eji.1830270808
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发表时间：
1997-08-01
影响因子：
5.4
通讯作者：
Moulon, C
中科院分区：
文献类型：
--
作者：
Vollmer, J;Fritz, M;Moulon, C
对镍（Ni）的超敏反应是人类接触性过敏的最常见表现。金属特异性T细胞在这种疾病中的作用已经得到了很好的证实，但对其激活所涉及的分子相互作用却知之甚少。我们研究了T细胞受体（TCR）库活化的T细胞与硫酸镍或硫酸镍处理的人血清白蛋白从6过敏患者。对于三个最高反应性的供体，我们发现TCR BV 17元件的强烈过度表达。这些供体之一的TCR测序揭示了AV 1的额外偏斜以及对BV 17互补决定区（CDR）3第95位的N区编码精氨酸的选择。由于精氨酸是不知道参与镍络合，我们假设，这种选择是由肽，而不是镍的接触。然而，BV 17的CDR 1含有独特的氨基酸组合（HDA），其与Ni结合蛋白或肽中的已知基序具有相似性。因此，我们提出，在BV 17过表达者中发现的严重超敏反应可能是Ni 2+离子将种系编码的BV 17 CDR 1环桥接到主要组织相容性复合物/肽复合物中的相应位点的结果，从而产生了弱TCR-肽接触的超抗原样增强。
Hypersensitivity to nickel (Ni) represents the most common manifestation of contact allergy in humans. The role of metal-specific T cells in this disease is well established, but the molecular interactions involved in their activation are poorly understood. We examined the T cell receptor (TCR) repertoire in T cells activated with either NiSO4 or NiSO4-treated human serum albumin from six allergic patients. For the three most hyperreactive donors, we found a strong over-represention of the TCR BV17 element. TCR sequencing for one of these donors revealed an additional skewing for AV1 as well as a selection for an N region encoded argine at position 95 of the BV17 complementarity determining region (CDR)3. Since Arg is not known to participate in Ni complexing, we suppose that this selection is driven by contacts with peptide rather than nickel. However, the CDR1 of BV17 contains a unique combination of amino acids (HDA) that bears similarities to known motifs in Ni-binding proteins or peptides. We therefore propose that the severe hypersensitivity reactions found in BV17 over-expressors may be the result of Ni2+ ions bridging the germ-line- encoded BV17 CDR1 loop to corresponding sites in the major histocompatibility complex/peptide complex and thereby creating a superantigen-like enhancement of weak TCR-peptide contacts.