Koch Institute for Integrative Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22373-80. doi: 10.1073/pnas.1012051108. Epub 2010 Dec 20.
Our goal is to provide a perspective on current understanding of the origins of specificity in immune reactions, a topic that has intrigued scientists for over a century. A fundamental property of adaptive immune responses is the ability to discriminate among an immense variety of substances by means of antibodies (Abs) and Ab-like receptors on T lymphocytes [T-cell receptors (TCRs)], each able to bind a particular chemical structure [the antigen (Ag)] and not, or only weakly, similar alternatives. Evidence has long existed, however, and has grown, especially recently, that while exhibiting remarkable specificity, many individual Abs and TCRs can also bind a variety of very different ligands. How can Ag recognition by these receptors exercise the great specificity for which they are renowned and yet react with a variety of different ligands (degeneracy)? We critically consider the mechanistic bases for this specificity/degeneracy enigma and also compare and contrast Ag recognition by Abs and TCRs.
我们的目标是提供一个视角，来看当前对免疫反应特异性起源的理解，这个主题困扰了科学家一个多世纪。适应性免疫反应的一个基本特性是通过抗体 (Abs) 和 T 淋巴细胞上的 Ab 样受体（T 细胞受体 (TCRs)）来区分大量不同的物质的能力，每个受体都能够结合特定的化学结构 [抗原 (Ag)]，而不能或只有弱地结合类似的替代物。然而，长期以来，尤其是最近，已经有证据表明，尽管表现出显著的特异性，许多单个 Abs 和 TCR 也可以结合各种非常不同的配体。这些受体如何识别 Ag，从而发挥它们的著名的特异性，同时又能与多种不同的配体（简并性）反应？我们批判性地考虑了这种特异性/简并性之谜的机制基础，并且还比较和对比了 Abs 和 TCRs 对 Ag 的识别。
