Warrender Annmaree K, Kelton William
Te Huataki Waiora School of Health, The University of Waikato, Hamilton, New Zealand.
Front Immunol. 2020 Aug 18;11:2016. doi: 10.3389/fimmu.2020.02016. eCollection 2020.
Polymorphic diversity in antibody constant domains has long been defined by allotypic motifs that cross react with the sera of other individuals. Improvements in sequencing technologies have led to the discovery of a large number of new allelic sequences that underlie this diversity. Many of the point mutations lie outside traditional allotypic motifs suggesting they do not elicit immunogenic responses. As antibodies play an important role in immune defense and biotechnology, understanding how this newly resolved diversity influences the function of antibodies is important. This review investigates the current known diversity of antibody alleles at a protein level for each antibody isotype as well as the kappa and lambda light chains. We focus on evidence emerging for how these mutations perturb antibody interactions with antigens and Fc receptors that are critical for function, as well as the influence this might have on the use of antibodies as therapeutics and reagents.
抗体恒定区的多态性多样性长期以来一直由与其他个体血清发生交叉反应的同种异型基序所定义。测序技术的进步导致发现了大量构成这种多样性基础的新等位基因序列。许多点突变位于传统同种异型基序之外，这表明它们不会引发免疫原性反应。由于抗体在免疫防御和生物技术中发挥着重要作用，了解这种新解析的多样性如何影响抗体功能非常重要。本综述研究了目前已知的每种抗体同种型以及κ和λ轻链在蛋白质水平上的抗体等位基因多样性。我们关注的证据表明，这些突变如何扰乱抗体与对抗功能至关重要的抗原和Fc受体的相互作用，以及这可能对抗体作为治疗剂和试剂的使用产生的影响。
