Decoding human-macaque interspecies differences in Fc-effector functions: The structural basis for CD16-dependent effector function in Rhesus macaques.
Decoding human-macaque interspecies differences in Fc-effector functions: The structural basis for CD16-dependent effector function in Rhesus macaques.
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DOI：
10.3389/fimmu.2022.960411
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
Fc介导的抗体效应器功能在免疫治疗和疫苗效力中发挥着重要作用，但由于物种差异，在动物模型中评估这些功能可能是具有挑战性的。猕猴，猕猴，猕猴(Mm)与人类有大约93%的序列同源性，但在适应性免疫系统中显示出重要的差异，这使得它们在验证依赖FC效应器功能的疗法和疫苗方面的使用变得复杂。与人类相比，猕猴只有一个低亲和力的FcγRIII受体CD16，它与人类FcγRIIIa在第158位具有相同的多态性，具有Ile158和Val158变异体。在这里，我们描述了mMFcγRIII中Ile/Val158多态的结构与功能的关系。我们的数据表明，MM FcγRIII等位基因变体对猕猴Ig G亚类的亲和力随着Fc和受体上的糖组成的变化而变化很大。然而，与FcγRIIIa中的人Phe/Val158多态不同，高亲和力变体对应于更大、更疏水的侧链ILE，即使它不直接参与结合界面。相反，这个侧链似乎调节了Fc/FcγRIII界面上的葡聚糖-葡聚糖相互作用。此外，受体上的葡聚糖组成的变化对Val158变异体有更大的影响，即对于寡注型多糖链和仅在Asn45和Asn162上的多糖链，Val158成为与Fc亲和力更高的变异体。这些结果不仅对更好地解释非人类灵长类研究有意义，而且对携带不同FcγRIIIa等位基因的人类效应细胞进行的研究也有意义。
Fc mediated effector functions of antibodies play important roles in immunotherapies and vaccine efficacy but assessing those functions in animal models can be challenging due to species differences. Rhesus macaques, Macaca mulatta (Mm) share approximately 93% sequence identity with humans but display important differences in their adaptive immune system that complicates their use in validating therapeutics and vaccines that rely on Fc effector functions. In contrast to humans, macaques only have one low affinity FcγRIII receptor, CD16, which shares a polymorphism at position 158 with human FcγRIIIa with Ile158 and Val158 variants. Here we describe structure-function relationships of the Ile/Val158 polymorphism in Mm FcγRIII. Our data indicate that the affinity of the allelic variants of Mm FcγRIII for the macaque IgG subclasses vary greatly with changes in glycan composition both on the Fc and the receptor. However, unlike the human Phe/Val158 polymorphism in FcγRIIIa, the higher affinity variant corresponds to the larger, more hydrophobic side chain, Ile, even though it is not directly involved in the binding interface. Instead, this side chain appears to modulate glycan-glycan interactions at the Fc/FcγRIII interface. Furthermore, changes in glycan composition on the receptor have a greater effect for the Val158 variant such that with oligomannose type glycans and with glycans only on Asn45 and Asn162, Val158 becomes the variant with higher affinity to Fc. These results have implications not only for the better interpretation of nonhuman primate studies but also for studies performed with human effector cells carrying different FcγRIIIa alleles.
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影响因子：
4
作者：
Falconer DJ;Subedi GP;Marcella AM;Barb AW
通讯作者：
Barb AW
影响因子：
7.3
作者：
Crowley AR;Osei-Owusu NY;Dekkers G;Gao W;Wuhrer M;Magnani DM;Reimann KA;Pincus SH;Vidarsson G;Ackerman ME
通讯作者：
Ackerman ME
影响因子：
2.1
作者：
Monera, Oscar D.;Sereda, Terrance J.;Hodges, Robert S.
通讯作者：
Hodges, Robert S.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
发表时间：
2012-04-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者：
Kim JH