Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes.
Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes.
复制标题
DOI：
10.1126/sciadv.ade7151
复制
发表时间：
2023-02-24
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
免疫伴侣Tapasin和TAP结合蛋白相关(TAPBPR)在抗原肽的优化和新生I类主要组织相容性复合体(MHC-I)分子的质量控制中起着关键作用。MHC-I蛋白的多态性质导致了对伴侣蛋白组装和细胞表面表达的一系列等位基因依赖，将伴侣蛋白介导的肽交换限制在一组受限的人类白细胞抗原(HLA)同种异型。在这里，我们展示和表征了一个鸡的TAPBPR同源基因和一个互补的HLA同种异型库之间的异种相互作用，相对于它的人类同源基因。我们发现，TAPBPR同源基因识别空的MHC-I具有更广泛的等位基因特异性，并通过维持接受分子的储存库促进肽交换。人TAPBPR的深度突变扫描进一步发现了与鸡相似的功能获得突变体，它可以增强原位表达的人类白细胞抗原-A*01：01，并在体外促进肽交换。这些结果强调了MHC-I和伴侣表面的多态位点可以被设计来操纵它们的相互作用，使伴侣介导的肽交换在疾病相关的HLA等位基因上实现。微调与伴侣的相互作用可以扩大MHC-I同种异型的范围，使其服从于抗原谱系的编辑。
Immunological chaperones tapasin and TAP binding protein, related (TAPBPR) play key roles in antigenic peptide optimization and quality control of nascent class I major histocompatibility complex (MHC-I) molecules. The polymorphic nature of MHC-I proteins leads to a range of allelic dependencies on chaperones for assembly and cell-surface expression, limiting chaperone-mediated peptide exchange to a restricted set of human leukocyte antigen (HLA) allotypes. Here, we demonstrate and characterize xeno interactions between a chicken TAPBPR ortholog and a complementary repertoire of HLA allotypes, relative to its human counterpart. We find that TAPBPR orthologs recognize empty MHC-I with broader allele specificity and facilitate peptide exchange by maintaining a reservoir of receptive molecules. Deep mutational scanning of human TAPBPR further identifies gain-of-function mutants, resembling the chicken sequence, which can enhance HLA-A*01:01 expression in situ and promote peptide exchange in vitro. These results highlight that polymorphic sites on MHC-I and chaperone surfaces can be engineered to manipulate their interactions, enabling chaperone-mediated peptide exchange on disease-relevant HLA alleles. Finetuning interactions with chaperones can broaden the scope of MHC-I allotypes that are amenable to antigen repertoire editing.
登录
查看更多内容
影响因子：
4.6
作者：
Smith C;Gras S;Brennan RM;Bird NL;Valkenburg SA;Twist KA;Burrows JM;Miles JJ;Chambers D;Bell S;Campbell S;Kedzierska K;Burrows SR;Rossjohn J;Khanna R
通讯作者：
Khanna R
影响因子：
14.9
作者：
Barker, Dominic J.;Maccari, Giuseppe;Georgiou, Xenia;Cooper, Michael A.;Flicek, Paul;Robinson, James;Marsh, Steven G. E.
通讯作者：
Marsh, Steven G. E.
DOI：
10.1073/pnas.2013554117
发表时间：
2020-11-10
影响因子：
11.1
作者：
Bashirova AA;Viard M;Naranbhai V;Grifoni A;Garcia-Beltran W;Akdag M;Yuki Y;Gao X;O'hUigin C;Raghavan M;Wolinsky S;Bream JH;Duggal P;Martinson J;Michael NL;Kirk GD;Buchbinder SP;Haas D;Goedert JJ;Deeks SG;Fellay J;Walker B;Goulder P;Cresswell P;Elliott T;Sette A;Carlson J;Carrington M
通讯作者：
Carrington M
DOI：
10.4049/jimmunol.1800343
发表时间：
2018-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Heredia JD;Park J;Brubaker RJ;Szymanski SK;Gill KS;Procko E
通讯作者：
Procko E
影响因子：
11.4
作者：
Chen, Mingnan;Bouvier, Marlene
通讯作者：
Bouvier, Marlene