Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles.
Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles.
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DOI：
10.1084/jem.178.1.27
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发表时间：
1993-07-01
期刊：
影响因子：
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通讯作者：
Strominger JL
中科院分区：
文献类型：
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作者：
Chicz RM;Urban RG;Gorga JC;Vignali DA;Lane WS;Strominger JL
从免疫亲和纯化的HLA-DR 2、DR 3、DR 4、DR 7和DR 8中酸提取天然加工的肽。使用质谱和Edman微测序的互补技术，从每个等位基因鉴定出> 200个独特的肽质量，范围从1，200至4，000道尔顿（长度为10-34个残基），并且获得总共201个肽序列。这些肽衍生自66种不同的来源蛋白质，并代表在氨基和羧基末端嵌套的组，平均长度为15-18个氨基酸。引人注目的是，大多数肽（> 85%）来源于与内吞/II类途径交叉的内源性蛋白质，尽管II类分子被认为主要在呈递外源性外源肽抗原中起作用。主要内源性肽来源于主要组织相容性复合物相关分子。一些来自外源牛血清蛋白的肽也与每个等位基因结合。鉴定了四个突出的混杂自身肽组（能够结合多个HLA-DR等位基因）以及84个等位基因特异性肽组。结合实验证实，混杂肽具有高亲和力的所有HLA-DR等位基因的结合沟检查。一个潜在的生理作用，这些内源性的自我肽作为免疫调节剂的细胞免疫反应进行了讨论。
Naturally processed peptides were acid extracted from immunoaffinity- purified HLA-DR2, DR3, DR4, DR7, and DR8. Using the complementary techniques of mass spectrometry and Edman microsequencing, > 200 unique peptide masses were identified from each allele, ranging from 1,200 to 4,000 daltons (10-34 residues in length), and a total of 201 peptide sequences were obtained. These peptides were derived from 66 different source proteins and represented sets nested at both the amino- and carboxy-terminal ends with an average length of 15-18 amino acids. Strikingly, most of the peptides (> 85%) were derived from endogenous proteins that intersect the endocytic/class II pathway, even though class II molecules are thought to function mainly in the presentation of exogenous foreign peptide antigens. The predominant endogenous peptides were derived from major histocompatibility complex-related molecules. A few peptides derived from exogenous bovine serum proteins were also bound to every allele. Four prominent promiscuous self- peptide sets (capable of binding to multiple HLA-DR alleles) as well as 84 allele-specific peptide sets were identified. Binding experiments confirmed that the promiscuous peptides have high affinity for the binding groove of all HLA-DR alleles examined. A potential physiologic role for these endogenous self-peptides as immunomodulators of the cellular immune response is discussed.