Morrison W I
Division of Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK.
Vet Parasitol. 2007 Aug 19;148(1):21-30. doi: 10.1016/j.vetpar.2007.05.007. Epub 2007 Jun 18.
The evolution of antigenically distinct pathogen strains that fail to cross-protect is well documented for pathogens controlled primarily by humoral immune responses. Unlike antibodies, which recognise native proteins, protective T cells can potentially recognise epitopes in a variety of proteins that are not necessarily displayed on the pathogen surface. Moreover, individual hosts of different MHC genotypes generally respond to different sets of epitopes. It is therefore less easy to envisage how strain restricted immunity can arise for pathogens controlled by T cell responses, particularly in antigenically complex parasites. Nevertheless, strain restricted immunity is clearly a feature of a number of parasitic infections, where immunity is known to be mediated by T cell responses. One such parasite is Theileria parva which induces potent CD8 T cell responses that play an important role in immunity. CD8 T cells specific for parasitized lymphoblasts exhibit strain specificity, which appears to correlate with the ability of parasite strains to cross-protect. Studies using recently identified T. parva antigens recognised by CD8 T cells have shown that the strain restricted nature of immunity is a consequence of the CD8 T cell response in individual animals being focused on a limited number of dominant polymorphic antigenic determinants. Responses in animals of different MHC genotypes are often directed to different parasite antigens, indicating that, at the host population level, a larger number of parasite proteins can serve as targets for the protective T cell response. Nevertheless, the finding that parasite strains show overlapping antigenic profiles, probably as a consequence of sexual recombination, suggests that induction of responses to an extended but limited set of antigens in individual animals may overcome the strain restricted nature of immunity.
对于主要由体液免疫反应控制的病原体，抗原性不同且无法交叉保护的病原体菌株的进化已有充分记录。与识别天然蛋白质的抗体不同，保护性T细胞可能识别多种蛋白质中的表位，这些表位不一定在病原体表面展示。此外，不同MHC基因型的个体宿主通常对不同的表位组合有反应。因此，对于由T细胞反应控制的病原体，尤其是抗原复杂的寄生虫，很难设想如何产生菌株限制性免疫。然而，菌株限制性免疫显然是许多寄生虫感染的一个特征，已知这些感染的免疫是由T细胞反应介导的。一种这样的寄生虫是微小泰勒虫，它诱导有效的CD8 T细胞反应，在免疫中起重要作用。对寄生淋巴母细胞特异的CD8 T细胞表现出菌株特异性，这似乎与寄生虫菌株的交叉保护能力相关。使用最近鉴定的CD8 T细胞识别的微小泰勒虫抗原进行的研究表明，免疫的菌株限制性本质是个体动物中CD8 T细胞反应集中于有限数量的显性多态性抗原决定簇的结果。不同MHC基因型动物的反应通常针对不同的寄生虫抗原，这表明在宿主群体水平上，更多的寄生虫蛋白质可以作为保护性T细胞反应的靶标。然而，寄生虫菌株显示出重叠抗原谱的发现，可能是由于有性重组，这表明在个体动物中诱导对一组扩展但有限的抗原的反应可能克服免疫的菌株限制性本质。
