Characterization of endogenous peptides bound to purified HLA-DR molecules and their absence from invariant chain-associated alpha beta dimers.
Characterization of endogenous peptides bound to purified HLA-DR molecules and their absence from invariant chain-associated alpha beta dimers.
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DOI：
10.4049/jimmunol.150.2.499
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发表时间：
1993-01
影响因子：
4.4
通讯作者：
J. Newcomb;P. Cresswell
中科院分区：
文献类型：
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作者：
J. Newcomb;P. Cresswell
我们已经检测了在体内与DRαβ二聚体结合的多肽和直接从DR11，DRW52纯合子B淋巴母细胞系中纯化的αβ不变(I)链复合体。用反相高效液相色谱法从细胞来源的α-β二聚体中分离纯化了9个主要多肽，并进行了序列测定。其中8种来自已知来源，包括内源和外源蛋白质。内源性多肽来源于分泌蛋白、跨膜蛋白胞外区和热休克蛋白。所有多肽的长度均为13~16个氨基酸。将这些DR结合多肽的一部分与其他已报道的DR结合多肽的序列进行比较表明，芳香族氨基酸加上来自它的七个碱性氨基酸的C-末端可能提供一个通用的但不是绝对的DR结合基序，额外的残基可能有助于DR等位基因的特异性。与α-β二聚体相反，未检测到与纯化的α-βI复合物结合的多肽。这些数据表明，细胞内与I链相关的α-β二聚体不与多肽结合，并在体内提供证据，表明I链在运输的早期阶段阻止了不适当的多肽与II类分子的结合。
We have examined peptides bound in vivo to DR alpha beta dimers and alpha beta-Invariant (I) chain complexes purified directly from a DR11, DRw52 homozygous B lymphoblastoid cell line. Nine major peptides were purified by reversed-phase HPLC from cell derived alpha beta dimers and sequenced. Eight of these were from known sources, including both endogenously synthesized and exogenous proteins. The endogenously derived peptides originated from secretory proteins, from the extracytoplasmic regions of transmembrane proteins, and from heat shock proteins. All of the peptides were from 13 to 16 amino acids in length. Comparison of the sequences of a subset of these DR-associated peptides with those of other reported DR-binding peptides suggests that an aromatic amino acid followed by a basic amino acid seven residues C-terminal from it may provide a generalizable, but not absolute, DR-binding motif, with additional residues possibly contributing to DR allelic specificity. In contrast to the alpha beta dimers, no peptides were detected bound to purified alpha beta I complexes. These data suggest that I chain-associated alpha beta dimers within the cell do not bind peptides, and provide in vivo evidence that I chain prevents the binding of inappropriate peptides to class II molecules during early stages of transport.