HLA class I-associated diseases with a suspected autoimmune etiology: HLA-B27 subtypes as a model system.
HLA class I-associated diseases with a suspected autoimmune etiology: HLA-B27 subtypes as a model system.
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疑似自身免疫病因的 HLA I 类相关疾病：HLA-B27 亚型作为模型系统
DOI：
10.1016/j.ejcb.2011.03.003
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发表时间：
2012
影响因子：
6.6
通讯作者：
Ziegler
中科院分区：
文献类型：
--
作者：
Uchanska-Ziegler;Fabian;Saenger;Ziegler
虽然大多数自身免疫性疾病与主要组织相容性复合体(MHC)II类等位基因有关，但其中一小部分疾病与选定的MHC I类基因表现出不同程度的关联，如某些人类HLA-A和HLA-B等位基因。然而，到目前为止，这些联系的基础仍然难以捉摸。可以通过比较等位基因的功能、生化和生物物理性质来获得理解，这些等位基因彼此之间的差异最小，但与给定疾病的差异却不同，如人类白细胞抗原-B*27：05和人类白细胞抗原-B*27：09，它们只有一个深埋在结合槽中的氨基酸残基(Asp116His)不同。我们采用了许多方法，包括X射线结晶学和同位素编辑红外光谱，研究了这两个亚型与多达10种不同多肽的复合体的生物物理特性。我们的发现表明，这些多肽的结合以及亚型的构象灵活性很大程度上受到C端肽残基相互作用的影响。特别是，与疾病相关的亚型HLA-B*27：05偏爱碱性C-末端多肽残基，而不是HLA-B*27：09。这一特性也是不同的人类白细胞抗原I类等位基因的唯一共同点，其中包括人类白细胞抗原-B*27：05、人类白细胞抗原-A*03：01或人类白细胞抗原-A*11：01，这些等位基因与怀疑有自身免疫病因的疾病有关。我们推测，由于这些等位基因的产物在胸腺中的阳性T细胞选择过程中与特定的肽集具有高亲和力结合的不寻常能力，因此参与了形成异常T细胞库的过程，该异常T细胞库易于获得自身免疫性疾病。
Although most autoimmune diseases are connected to major histocompatibility complex (MHC) class II alleles, a small number of these disorders exhibit a variable degree of association with selected MHC class I genes, like certain human HLA-A and HLA-B alleles. The basis for these associations, however, has so far remained elusive. An understanding might be obtained by comparing functional, biochemical, and biophysical properties of alleles that are minimally distinct from each other, but are nevertheless differentially associated to a given disease, like the HLA-B*27:05 and HLA-B*27:09 antigens, which differ only by a single amino acid residue (Asp116His) that is deeply buried within the binding groove. We have employed a number of approaches, including X-ray crystallography and isotope-edited infrared spectroscopy, to investigate biophysical characteristics of the two HLA-B27 subtypes complexed with up to ten different peptides. Our findings demonstrate that the binding of these peptides as well as the conformational flexibility of the subtypes is greatly influenced by interactions of the C-terminal peptide residue. In particular, a basic C-terminal peptide residue is favoured by the disease-associated subtype HLA-B*27:05, but not by HLA-B*27:09. This property appears also as the only common denominator of distinct HLA class I alleles, among them HLA-B*27:05, HLA-A*03:01 or HLA-A*11:01, that are associated with diseases suspected to have an autoimmune etiology. We postulate here that the products of these alleles, due to their unusual ability to bind with high affinity to a particular peptide set during positive T cell selection in the thymus, are involved in shaping an abnormal T cell repertoire which predisposes to the acquisition of autoimmune diseases.
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影响因子：
5.5
作者：
C. López;R. Díaz
通讯作者：
R. Díaz
影响因子：
3.6
作者：
E. Huseby;J. Kappler;P. Marrack
通讯作者：
E. Huseby;J. Kappler;P. Marrack
影响因子：
16.8
作者：
B. Uchánska‐Ziegler;A. Ziegler
通讯作者：
B. Uchánska‐Ziegler;A. Ziegler
影响因子：
56.9
作者：
Huh, GS;Boulanger, LM;Shatz, CJ
通讯作者：
Shatz, CJ
多态性嗅觉受体基因和HLA基因座构成扩展单倍型
DOI：
--
发表时间：
2000
期刊：
影响因子：
--
作者：
A. Ziegler;A. Ehlers;S. Forbes;J. Trowsdale;B. Uchánska‐Ziegler;A. Volz;R. Younger;S. Beck
通讯作者：
S. Beck