Allotype-Specific Glycosylation and Cellular Localization of Human Leukocyte Antigen Class I Proteins.
Allotype-Specific Glycosylation and Cellular Localization of Human Leukocyte Antigen Class I Proteins.
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DOI：
10.1021/acs.jproteome.1c00466
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发表时间：
2021-09-03
影响因子：
4.4
通讯作者：
Heck AJR
中科院分区：
文献类型：
--
作者：
Hoek M;Demmers LC;Wu W;Heck AJR
人类白细胞抗原（HLA）复合物在细胞表面呈递抗原是免疫应答的关键过程。α链含有肽结合沟，是蛋白质组中最具多态性的蛋白质之一。所有的HLA I类α链都携带一个保守的N-糖基化位点，但对其性质和功能知之甚少。在这里，我们报告的N-糖基化HLA I类分子的功能的深入表征。我们观察到不同的HLA-A α链携带相似的糖基化，与HLA-B、HLA-C和HLA-F α链明显不同。虽然HLA-A显示出最广泛的聚糖特征，但HLA-B α链携带的大多是成熟聚糖，HLA-C和HLA-F α链主要携带高甘露糖聚糖。我们预期这些糖基化特征与HLA复合物的细胞定位直接相关。事实上，分析来自粗血浆和内膜富集级分的HLA I类复合物证实，大多数HLA-B复合物可以在质膜处发现，而大多数HLA-C和HLA-F分子存在于内质网和高尔基体膜中，并且HLA-A分子更均匀地分布在这些细胞区室中。当分析免疫肽组学的肽抗原递呈时，应考虑HLA分子的这种同种异型特异性细胞分布。
Presentation of antigens by human leukocyte antigen (HLA) complexes at the cell surface is a key process in the immune response. The α-chain, containing the peptide-binding groove, is one of the most polymorphic proteins in the proteome. All HLA class I α-chains carry a conserved N-glycosylation site, but little is known about its nature and function. Here, we report an in-depth characterization of N-glycosylation features of HLA class I molecules. We observe that different HLA-A α-chains carry similar glycosylation, distinctly different from the HLA-B, HLA-C, and HLA-F α-chains. Although HLA-A displays the broadest variety of glycan characteristics, HLA-B α-chains carry mostly mature glycans, and HLA-C and HLA-F α-chains carry predominantly high-mannose glycans. We expected these glycosylation features to be directly linked to cellular localization of the HLA complexes. Indeed, analyzing HLA class I complexes from crude plasma and inner membrane-enriched fractions confirmed that most HLA-B complexes can be found at the plasma membrane, while most HLA-C and HLA-F molecules reside in the endoplasmic reticulum and Golgi membrane, and HLA-A molecules are more equally distributed over these cellular compartments. This allotype-specific cellular distribution of HLA molecules should be taken into account when analyzing peptide antigen presentation by immunopeptidomics.
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影响因子：
30.5
作者：
Garcia-Beltran WF;Hölzemer A;Martrus G;Chung AW;Pacheco Y;Simoneau CR;Rucevic M;Lamothe-Molina PA;Pertel T;Kim TE;Dugan H;Alter G;Dechanet-Merville J;Jost S;Carrington M;Altfeld M
通讯作者：
Altfeld M
影响因子：
2.6
作者：
Gough SC;Simmonds MJ
通讯作者：
Simmonds MJ
影响因子：
32.4
作者：
Abelin JG;Keskin DB;Sarkizova S;Hartigan CR;Zhang W;Sidney J;Stevens J;Lane W;Zhang GL;Eisenhaure TM;Clauser KR;Hacohen N;Rooney MS;Carr SA;Wu CJ
通讯作者：
Wu CJ
影响因子：
3.6
作者：
Armony, Gad;Heck, Albert J. R.;Wu, Wei
通讯作者：
Wu, Wei
影响因子：
32.4
作者：
Goulder PJ;Walker BD
通讯作者：
Walker BD