Wallace M E, Bryden M, Cose S C, Coles R M, Schumacher T N, Brooks A, Carbone F R
Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria, Australia.
Immunity. 2000 May;12(5):547-56. doi: 10.1016/s1074-7613(00)80206-x.
The enormous diversity of the T cell pool makes it difficult to determine whether inherent biases in the naive TCR repertoire can influence T cell responsiveness. In C57BL/6 mice the cytotoxic T lymphocyte response to an immunodominant HSV-1 determinant (gB) is characterized by a prominent bias in Vbeta element usage, associated with a conserved and preferentially D element-encoded CDR3 sequence. Comparison of naive and gB-specific T cell populations revealed a similar enrichment of germline D element-encoded CDR3 sequences in the preimmune repertoire. Strikingly, eliminating the germline coding of the gB-specific CDR3 sequence caused an almost complete loss of the dominant subset of gB-specific T cells, illustrating that CDR3 biases can significantly alter both the composition and strength of an immune response.
T细胞库的巨大多样性使得难以确定初始TCR库中的固有偏向是否会影响T细胞反应性。在C57BL/6小鼠中，细胞毒性T淋巴细胞对免疫显性的单纯疱疹病毒1型（HSV-1）决定簇（gB）的反应，其特征在于Vβ元件使用存在显著偏向，这与保守且优先由D元件编码的互补决定区3（CDR3）序列相关。对初始和gB特异性T细胞群体的比较显示，在免疫前库中，种系D元件编码的CDR3序列有类似的富集。引人注目的是，消除gB特异性CDR3序列的种系编码几乎导致gB特异性T细胞优势亚群完全丧失，这表明CDR3偏向可显著改变免疫反应的组成和强度。
