在以七鳃鳗和盲鳗为代表的无颌类脊椎动物中, 虽然发现了与有颌类脊椎动物T细胞受体(T-cell receptors, TLRs)、B细胞受体 (B-cell receptors, BCRs)可变区具有相似结构的先天性免疫受体, 却从未发现有颌类脊椎动物适应性免疫系统的核心组分: TCRs、BCRs、组织相容性复合体 (Major histocompatibility complex, MHC)。因此, 长期以来, 人们一直认为适应性免疫系统只存在于有颌类脊椎动物中。但最近的一项发现彻底改变了这一传统观念, 即在无颌类脊椎动物中, 存在一种新型可变淋巴细胞受体VLRs(Variable lymphocyte receptors), VLRs通过改变亮氨酸富集序列LRRs(Leucine-rich repeats)的插入情况, 实现对特异性抗原的高效识别。晶体衍射分析发现, 盲鳗的VLRs呈现一种“马蹄”型结构, 抗原结合位点则位于“马蹄”的凹面区。分泌型的VLRs以四聚体或五聚体的形式识别、结合特异性抗原。综上所述, 无颌类和有颌类脊椎动物应用不同的抗原识别系统完成适应性免疫反应。文章对近年来无颌类脊椎动物适应性免疫系统相关分子的研究进展加以概述, 为揭示适应性免疫系统起源与进化问题提供有益参考。

Abstract: Extant jawless vertebrates, represented by lampreys and hagfishes, have innate immune receptors with variable domains structurally resembling T/B-cell receptors. However, they lack cardinal elements of adaptive immunity shared by all jawed vertebrates: T/B-cell receptors and major histocompati?bility complex molecules. Thus, it was widely believed that adaptive immu?nity is unique to jawed vertebrates. Recently, this belief was overturned by the discovery of agnathan antigen receptors named variable lymphocyte receptors. These receptors generate diver?sity in their antigen-binding sites through assembling highly diverse leucine-rich repeat modules. The crystal structures of hagfish variable lymphocyte receptor monomers indicate that they adopt a horseshoe-shaped structure and likely bind antigens through the hypervariable concave surface. Secreted variable lymphocyte receptors form pentamers or tetramers of dimers bind antigens with high specificity and avidity. The fact indicates that jawed and jawless vertebrates have developed antigen receptors independently. This paper provides valuable clues for studying of the origin and evolution of adaptive immunity system.