Antigen nature and complexity influence human antibody light chain usage and specificity.
Antigen nature and complexity influence human antibody light chain usage and specificity.
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DOI：
10.1016/j.vaccine.2016.04.040
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发表时间：
2016-05-27
期刊：
影响因子：
5.5
通讯作者：
James JA
中科院分区：
文献类型：
--
作者：
Smith K;Shah H;Muther JJ;Duke AL;Haley K;James JA
人抗体由一条重链和两条可能的轻链（κ或λ）之一组成。在这里，我们通过测量来自接种Pneumovax 23后获得的抗体分泌细胞的人单克隆抗体中的轻链使用，测试了这两种可能的轻链如何影响对多糖和蛋白质抗原的总体抗体应答。值得注意的是，我们发现，个人显示限制轻链使用某些血清型，λ抗体具有不同的特异性和交叉反应性模式比κ抗体。因此，在单克隆（7 kappa，无lambda）和血清水平（145 μg/mL kappa，2.82 μg/mL lambda）下，细胞壁多糖抗体几乎总是kappa。分析肺炎球菌参考血清007 sp对12种肺炎球菌血清型的轻链使用情况，并对其进行了充分表征。与单克隆水平的结果相似，某些血清型倾向于支持其中一条轻链（14和19 A，λ; 6 A和23 F，κ）。我们还探讨了在血清水平上对各种抗原的轻链使用的差异。我们检测了白喉毒素突变体CRM 197和EB病毒蛋白EBNA-1的血清抗体。这些反应倾向于kappa显性（平均kappa/lambda比值分别为4.52和9.72）。对流感疫苗的反应更加平衡，κ-λ比平均值有轻微的毒株变化：季节性H1N1，1.1; H3 N2，0.96; B，0.91。我们的结论是，抗原表位有限的倾向于产生抗体与限制轻链的使用，在大多数人中，抗体与λ轻链具有特异性不同，并与κ-含抗体互补。
Human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). Here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with Pneumovax23. Remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies have different specificities and modes of cross-reactivity than kappa antibodies. Thus, at both the monoclonal (7 kappa, no lambda) and serum levels (145 μg/mL kappa, 2.82 μg/mL lambda), antibodies to cell wall polysaccharide were nearly always kappa. The pneumococcal reference serum 007sp was analyzed for light chain usage to 12 pneumococcal serotypes for which it is well characterized. Similar to results at the monoclonal level, certain serotypes tended to favor one of the light chains (14 and 19A, lambda; 6A and 23F, kappa). We also explored differences in light chain usage at the serum level to a variety of antigens. We examined serum antibodies to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1. These responses tended to be kappa dominant (average kappa-to-lambda ratios of 4.52 and 9.72 respectively). Responses to the influenza vaccine were more balanced with kappa-to-lambda ratio averages having slight strain variations: seasonal H1N1, 1.1; H3N2, 0.96; B, 0.91. We conclude that antigens with limited epitopes tend to produce antibodies with restricted light chain usage and that in most individuals, antibodies with lambda light chains have specificities different and complementary to kappa-containing antibodies.