Navoa Josephine Anne D, Laal Suman, Pirofski Liise-Anne, McLean Gary R, Dai Zhongdong, Robbins John B, Schneerson Rachel, Casadevall Arturo, Glatman-Freedman Aharona
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, New York 10461, USA.
Clin Diagn Lab Immunol. 2003 Jan;10(1):88-94. doi: 10.1128/cdli.10.1.88-94.2003.
Arabinomannan (AM) is a polysaccharide antigen of the mycobacterial capsule. However, it is uncertain whether AM constitutes an immunologically distinct fraction of Mycobacterium tuberculosis. In this study, we analyzed the repertoire and specificity of antibodies to AM by using AM-binding murine monoclonal antibodies (MAbs) and human serum samples. Murine MAbs were found to be diverse in their specificity to AM and cross-reactivity with other arabinose-containing mycobacterial polysaccharides, with MAb 9d8 binding exclusively to AM. Human antibodies to AM were detected in serum samples from patients with pulmonary tuberculosis (TB), as well as in those from healthy, purified protein derivative-negative controls, with significantly higher titers among patients. The binding of human antibodies to AM was inhibited by MAb 9d8 in three patients with TB but not in controls. MAb 5c11, which recognizes other mycobacterial arabinose-containing carbohydrates in addition to AM, inhibited the binding of serum samples from 75% of patients and 76% of controls. Analysis of human antibodies with murine MAbs to human V(H) determinants demonstrated diversity among antibodies to AM with qualitative and quantitative differences compared with antibodies to lipoarabinomannan. In summary, our study suggests that antibodies to AM are diverse and heterogeneous with respect to antigen recognition and V(H) determinant expression, with human serum samples containing different subsets of antibodies to AM with the specificities of AM-binding murine MAbs. One MAb and a subset of human antibodies bind AM specifically, suggesting that this polysaccharide is antigenically distinct and is expressed in human infection.
阿拉伯甘露聚糖（AM）是分枝杆菌荚膜的一种多糖抗原。然而，AM是否构成结核分枝杆菌的一个免疫上独特的部分尚不确定。在本研究中，我们通过使用结合AM的鼠单克隆抗体（MAb）和人血清样本分析了抗AM抗体的库和特异性。发现鼠MAb对AM的特异性及其与其他含阿拉伯糖的分枝杆菌多糖的交叉反应性各不相同，其中MAb 9d8仅与AM结合。在肺结核（TB）患者的血清样本以及健康的纯化蛋白衍生物阴性对照的血清样本中检测到了人抗AM抗体，患者中的滴度显著更高。在三名TB患者中，MAb 9d8抑制了人抗体与AM的结合，但在对照中未观察到这种情况。MAb 5c11除了识别AM外还识别其他含阿拉伯糖的分枝杆菌碳水化合物，它抑制了75%的患者和76%的对照的血清样本的结合。用鼠MAb对人V(H)决定簇分析人抗体表明，与抗脂阿拉伯甘露聚糖抗体相比，抗AM抗体在抗体多样性方面存在定性和定量差异。总之，我们的研究表明，抗AM抗体在抗原识别和V(H)决定簇表达方面是多样且异质的，人血清样本中含有不同亚群的具有AM结合鼠MAb特异性的抗AM抗体。一种MAb和一部分人抗体特异性结合AM，表明这种多糖在抗原性上是独特的，并且在人类感染中表达。
