Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
Nat Rev Immunol. 2019 Jun;19(6):355-368. doi: 10.1038/s41577-019-0126-7.
Antibodies are essential components of adaptive immunity. A typical antibody repertoire comprises an enormous diversity of antigen-binding specificities, which are generated by the genetic processes of recombination and mutation. Accumulating evidence suggests that the immune system can exploit additional strategies to diversify the repertoire of antigen specificities. These unconventional mechanisms exclusively target the antigen-binding sites of immunoglobulins and include the insertion of large amino acid sequences, post-translational modifications, conformational heterogeneity and use of nonprotein cofactor molecules. Here, we describe the different unconventional routes for diversification of antibody specificities. Furthermore, we highlight how the immune system has a much greater level of adaptability and plasticity than previously anticipated, which goes far beyond that encoded in the genome or generated by the acquisition of somatic mutations.
抗体是适应性免疫的重要组成部分。典型的抗体库由大量具有抗原结合特异性的多样性组成，这些特异性是通过重组和突变的遗传过程产生的。越来越多的证据表明，免疫系统可以利用额外的策略来使抗原特异性的库多样化。这些非常规机制专门针对免疫球蛋白的抗原结合位点，包括插入大的氨基酸序列、翻译后修饰、构象异质性和使用非蛋白辅助因子分子。在这里，我们描述了抗体特异性多样化的不同非常规途径。此外，我们还强调了免疫系统的适应性和可塑性比以前预期的要高得多，这远远超出了基因组编码或通过获得体细胞突变所产生的适应性和可塑性。
