PREDOMINANT NATURALLY PROCESSED PEPTIDES BOUND TO HLA-DR1 ARE DERIVED FROM MHC-RELATED MOLECULES AND ARE HETEROGENEOUS IN SIZE
PREDOMINANT NATURALLY PROCESSED PEPTIDES BOUND TO HLA-DR1 ARE DERIVED FROM MHC-RELATED MOLECULES AND ARE HETEROGENEOUS IN SIZE
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DOI：
10.1038/358764a0
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发表时间：
1992-08-27
期刊：
影响因子：
64.8
通讯作者：
STROMINGER, JL
中科院分区：
文献类型：
--
作者：
CHICZ, RM;URBAN, RG;STROMINGER, JL
与I类分子结合的多肽长度为8-10个氨基酸，并具有代表与给定I类分子结合的多肽的结合基序1-4。在唯一发表的与II类分子(小鼠I-A(B)和I-E(B))结合的自然加工多肽的研究中，这些多肽更长(13-17个氨基酸)，具有不同的羧基末端，但精确的氨基末端截断5。在这里，我们报告了用高效液相色谱、质谱学和微测序分析鉴定与人类白细胞抗原-DR1结合的酸洗脱肽。多肽的相对分子质量在1,602-2,996(13-25个残基)之间变化，最丰富的个体M(R)值在1,700-1,800之间，对应的平均多肽长度为15个残基。获得了来自5个表位的20个肽的完整序列数据，除1个表位外，其余均来自自身蛋白。这些多肽代表在N-末端和C-末端均嵌套的集合。结合实验证实，所有分离的多肽都与DR1的沟槽具有较高的亲和力。与已知的35个已知的人类白细胞抗原-DR1结合多肽的序列比对显示了一个可能的基序。尽管与II类分子结合的多肽可能有一些相关的特征(由于非多态的HLA-DR阿尔法链)，考虑到与不同等位基因的简并结合6，但人类白细胞抗原-DRβ链中的特定氨基酸可能定义了多肽结合的等位基因特异性。
PEPTIDES bound to class I molecules are 8-10 amino acids long, and possess a binding motif representative of peptides that bind to a given class I allele1-4. In the only published study of naturally processed peptides bound to class II molecules (mouse I-A(b) and I-E(b)), these peptides were longer (13-17 amino acids) and had heterogenous carboxy terminals but precise amino-terminal truncations5. Here we report the characterization of acid-eluted peptides bound to HLA-DR1 by high-performance liquid chromatography, mass spectrometry and microsequencing analyses. The relative molecular masses of the peptides varied between 1,602 and 2,996 (13-25 residues), the most abundant individual M(r) values being between 1,700 and 1,800, corresponding to an average peptide length of 15 residues. Complete sequence data were obtained for twenty peptides derived from five epitopes, of which all but one were from self proteins. These peptides represented sets nested at both the N- and C-terminal ends. Binding experiments confirmed that all of the isolated peptides had high affinity for the groove of DR1. Alignment of the peptides bound to HLA-DR1 and the sequences of 35 known HLA-DR1-binding peptides revealed a putative motif. Although peptides bound to class II molecules may have some related features (due to the nonpolymorphic HLA-DR alpha-chain), accounting for degenerate binding to different alleles6, particular amino acids in the HLA-DR beta-chains presumably define allelic specificity of peptide binding.