Lipopeptides: a novel antigen repertoire presented by major histocompatibility complex class I molecules
Lipopeptides: a novel antigen repertoire presented by major histocompatibility complex class I molecules
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DOI：
10.1111/imm.12646
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发表时间：
2016-10
期刊：
影响因子：
6.4
通讯作者：
D. Morita;M. Sugita
中科院分区：
文献类型：
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作者：
D. Morita;M. Sugita
免疫后修饰的肽，例如含有磷酸化或O-糖基化丝氨酸/苏氨酸残基的肽，可以通过MHC I类分子呈递给细胞毒性T淋巴细胞（CTL）。这些修饰的肽中的大多数以与未修饰的肽类似的方式被捕获在MHC I类沟中。N-肉豆蔻酰化5聚体脂肽最近被鉴定为MHC I类呈递抗原的新化学类别。发现恒河猴经典MHC I类等位基因Mamu B*098能够结合N-肉豆蔻酰化脂肽并将其呈递给CTL。Mamu B*098：脂肽复合物的高分辨率X射线晶体学分析显示，脂肽配体的肉豆蔻基以及保守的C末端丝氨酸残基起锚定作用，而位于脂肽中间的三个氨基酸残基的短片段仅暴露于外部，具有直接与特异性T细胞受体相互作用的潜力。因此，脂肽-配体与MHC I类和T细胞受体相互作用的模式是新的，与MHC I类呈递肽的模式有根本区别。另一个脂肽呈递MHC I类等位基因现在已经被鉴定，这使我们预测MHC I类分子可以在功能基础上分为两组：一组呈递长肽，另一组呈递短脂肽。由于病毒蛋白的N-豆蔻酰化通常与发病机制有关，因此能够感测N-豆蔻酰化的CTL可能用于控制致病性病毒，从而提高了开发新型脂肽疫苗的可能性。
Post‐translationally modified peptides, such as those containing either phosphorylated or O‐glycosylated serine/threonine residues, may be presented to cytotoxic T lymphocytes (CTLs) by MHC class I molecules. Most of these modified peptides are captured in the MHC class I groove in a similar manner to that for unmodified peptides. N‐Myristoylated 5‐mer lipopeptides have recently been identified as a novel chemical class of MHC class I‐presented antigens. The rhesus classical MHC class I allele, Mamu‐B*098, was found to be capable of binding N‐myristoylated lipopeptides and presenting them to CTLs. A high‐resolution X‐ray crystallographic analysis of the Mamu‐B*098:lipopeptide complex revealed that the myristic group as well as conserved C‐terminal serine residue of the lipopeptide ligand functioned as anchors, whereas the short stretch of three amino acid residues located in the middle of the lipopeptides was only exposed externally with the potential to interact directly with specific T‐cell receptors. Therefore, the modes of lipopeptide–ligand interactions with MHC class I and with T‐cell receptors are novel and fundamentally distinct from that for MHC class I‐presented peptides. Another lipopeptide‐presenting MHC class I allele has now been identified, leading us to the prediction that MHC class I molecules may be separated on a functional basis into two groups: one presenting long peptides and the other presenting short lipopeptides. Since the N‐myristoylation of viral proteins is often linked to pathogenesis, CTLs capable of sensing N‐myristoylation may serve to control pathogenic viruses, raising the possibility for the development of a new type of lipopeptide vaccine.