Benaroya Research Institute at Virginia Mason, Seattle, WA 98101-2795, USA.
J Immunol. 2012 Mar 15;188(6):2537-44. doi: 10.4049/jimmunol.1102190. Epub 2012 Feb 10.
The frequency of epitope-specific naive CD4(+) T cells in humans has not been extensively examined. In this study, a systematic approach was used to examine the frequency of CD4(+) T cells that recognize the protective Ag of Bacillus anthracis in both anthrax vaccine-adsorbed vaccinees and nonvaccinees with HLA-DRB1*01:01 haplotypes. Three epitopes were identified that had distinct degrees of immunodominance in subjects that had received the vaccine. Average naive precursor frequencies of T cells specific for these different epitopes in the human repertoire ranged from 0.2 to 10 per million naive CD4(+) T cells, which is comparable to precursor frequencies observed in the murine repertoire. Frequencies of protective Ag-specific T cells were two orders of magnitude higher in immunized subjects than in nonvaccinees. The frequencies of epitope-specific memory CD4(+) T cells in vaccinees were directly correlated with the frequencies of precursors in the naive repertoire. At the level of TCR usage, at least one preferred Vβ in the naive repertoire was present in the memory repertoire. These findings implicate naive frequencies as a crucial factor in shaping the epitope specificity of memory CD4(+) T cell responses.
人类中表位特异性幼稚 CD4(+) T 细胞的频率尚未被广泛研究。在这项研究中，采用系统的方法来检测识别炭疽芽孢杆菌保护性抗原的 CD4(+) T 细胞在炭疽疫苗吸附疫苗接种者和具有 HLA-DRB1*01:01 单倍型的非疫苗接种者中的频率。鉴定出了三个在接受过疫苗接种的受试者中具有不同免疫优势的表位。人类免疫库中针对这些不同表位的 T 细胞幼稚前体频率的平均值范围从每百万幼稚 CD4(+) T 细胞的 0.2 到 10 个，与在鼠类免疫库中观察到的前体频率相当。在免疫接种的受试者中，保护性抗原特异性 T 细胞的频率比非疫苗接种者高两个数量级。疫苗接种者中表位特异性记忆 CD4(+) T 细胞的频率与幼稚库中的前体频率直接相关。在 TCR 使用水平上，幼稚库中至少有一种优先的 Vβ 存在于记忆库中。这些发现表明幼稚频率是塑造记忆 CD4(+) T 细胞反应表位特异性的关键因素。
