Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724 and the BIO-5 Institute, University of Arizona, Tucson,AZ 85719.
Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia.
J Immunol. 2010 Mar 15;184(6):2958-2965. doi: 10.4049/jimmunol.0903493. Epub 2010 Feb 17.
The diversity of the pathogen-specific T cell repertoire is believed to be important in allowing recognition of different pathogen epitopes and their variants and thereby reducing the opportunities for mutation-driven pathogen escape. However, the extent to which the TCR repertoire can be manipulated by different vaccine strategies so as to obtain broad diversity and optimal protection is incompletely understood. We have investigated the influence of the infectious/inflammatory context on the TCR diversity of the CD8(+) T cell response specific for the immunodominant epitope in C57BL/6 mice, derived from glycoprotein B of HSV-1. To that effect, we compared TCR V segment utilization, CDR3 length, and sequence diversity of the response to natural HSV-1 infection with those elicited by either Listeria monocytogenes or vaccinia virus expressing the immunodominant epitope in C57BL/6 mice. We demonstrate that although the type of infection in which the epitope was encountered can influence the magnitude of the CD8(+) T cell responses, TCR beta-chain repertoires did not significantly differ among the three infections. These results suggest that widely different live vaccine vectors may have little impact upon the diversity of the induced CTL response, which has important implications for the design of live CTL vaccine strategies against acute and chronic infections.
病原体特异性 T 细胞库的多样性被认为对于识别不同病原体表位及其变体非常重要,从而减少了病原体突变逃逸的机会。然而,不同疫苗策略对 T 细胞受体库的操纵程度,以便获得广泛的多样性和最佳的保护作用,还不完全清楚。我们研究了感染/炎症背景对源自 HSV-1 糖蛋白 B 的 C57BL/6 小鼠中针对免疫优势表位的 CD8(+)T 细胞反应的 TCR 多样性的影响。为此,我们比较了自然 HSV-1 感染与李斯特菌或表达免疫优势表位的牛痘病毒感染引起的反应的 TCR V 区利用、CDR3 长度和序列多样性。我们证明,尽管遇到表位的感染类型会影响 CD8(+)T 细胞反应的强度,但三种感染之间的 TCRβ链库并没有显著差异。这些结果表明,广泛不同的活疫苗载体可能对诱导的 CTL 反应的多样性影响不大,这对于针对急性和慢性感染的活 CTL 疫苗策略的设计具有重要意义。