Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands.
Eur J Immunol. 2009 Nov;39(11):3031-41. doi: 10.1002/eji.200939619.
Although CD1 proteins are known to present mycobacterial lipid antigens to T cells, there is little understanding of the in vivo behavior of T cells restricted by CD1a, CD1b and CD1c, and the relative immunogenicity and immunodominance of individual lipids within the total array of lipids that comprise a bacterium. Because bovines express multiple CD1 proteins and are natural hosts of Mycobacterium bovis and Mycobacterium avium paratuberculosis (MAP), we used them as a new animal model of CD1 function. Here, we report the surprisingly divergent responses against lipids produced by these two pathogens during infection. Despite considerable overlap in lipid content, only three out of 69 animals cross-react with M. bovis and MAP total lipid preparations. The unidentified immunodominant compound of M. bovis is a hydrophilic compound, whereas the immunodominant lipid of MAP is presented by CD1b and was identified as glucose monomycolate (GMM). The preferential recognition of GMM antigen by MAP-infected cattle may be explained by the higher expression of GMM by MAP than by M. bovis. The bacterial species-specific nature of the CD1-restricted, adaptive T-cell response affects the approach to development of lipid based immunodiagnostic tests.
虽然已知 CD1 蛋白可将分枝杆菌脂质抗原呈递给 T 细胞，但对于 CD1a、CD1b 和 CD1c 限制的 T 细胞的体内行为，以及构成细菌的总脂质阵列中各个脂质的相对免疫原性和免疫优势，人们知之甚少。由于牛表达多种 CD1 蛋白，并且是牛分枝杆菌和牛分枝杆菌副结核分枝杆菌（MAP）的天然宿主，因此我们将其用作 CD1 功能的新型动物模型。在这里，我们报告了在感染过程中针对这两种病原体产生的脂质产生的惊人不同的反应。尽管脂质含量有很大重叠，但在 69 只动物中，只有 3 只与牛分枝杆菌和 MAP 总脂质制剂发生交叉反应。牛分枝杆菌的未鉴定免疫优势化合物是一种亲水化合物，而 MAP 的免疫优势脂质由 CD1b 呈递，并被鉴定为葡萄糖单胞酸酯（GMM）。MAP 感染牛对 GMM 抗原的优先识别可以用 MAP 比牛分枝杆菌表达更高的 GMM 来解释。CD1 限制的适应性 T 细胞反应的细菌种特异性会影响基于脂质的免疫诊断测试的开发方法。
