Cole G A, Hogg T L, Woodland D L
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105.
Int Immunol. 1994 Nov;6(11):1767-75. doi: 10.1093/intimm/6.11.1767.
We have used Sendai virus infection of C57BL/6 mice as a model with which to study the T cell response to a single MHC class I epitope. Cells taken from the bronchoalveolar lavage or restimulated in vitro from the mediastinal lymph nodes of virus-infected mice were strongly cytotoxic for a single nucleoprotein epitope, NP324-332/Kb. To correlate TCR usage with specificity for the immunodominant epitope, we generated T cell hybridomas from the bronchoalveolar lavage and mediastinal lymph node cells of C57BL/6 mice at the peak of infection. Altogether, 20 hybridomas were identified that specifically secreted IL-2 in response to NP324-332-pulsed L929-Kb cells. TCR usage in this panel of hybridomas was extremely diverse. Over half of the available J beta and V beta elements present in the C57BL/6 strain of mouse were represented in the hybridomas. Similarly, V alpha usage was also diverse and all 12 of the alpha chains sequenced used distinct J alpha elements. The only relatively conserved feature of the TCR in these hybridomas was the presence of an arginine residue in the junctions of 70% of the beta chains. These data demonstrate that a diverse repertoire of TCR is able to recognize a single MHC class I epitope. Moreover, the data demonstrate that mice make use of this potential diversity in the primary response to a natural viral infection.
我们利用仙台病毒感染C57BL/6小鼠作为模型,来研究T细胞对单个MHC I类表位的反应。从支气管肺泡灌洗中获取的细胞,或从病毒感染小鼠的纵隔淋巴结中体外再刺激得到的细胞,对单个核蛋白表位NP324 - 332/Kb具有强烈的细胞毒性。为了将TCR使用情况与对免疫显性表位的特异性相关联,我们在感染高峰期从C57BL/6小鼠的支气管肺泡灌洗和纵隔淋巴结细胞中生成了T细胞杂交瘤。总共鉴定出20个杂交瘤,它们在接触NP324 - 332脉冲的L929 - Kb细胞时特异性分泌白细胞介素-2。这组杂交瘤中的TCR使用情况极为多样。C57BL/6小鼠品系中存在的可用Jβ和Vβ元件,超过一半在杂交瘤中有所体现。同样,Vα的使用情况也多样,所有12条测序的α链都使用了不同的Jα元件。这些杂交瘤中TCR唯一相对保守的特征是,70%的β链连接处存在一个精氨酸残基。这些数据表明,多种TCR能够识别单个MHC I类表位。此外,数据表明小鼠在对自然病毒感染的初次反应中利用了这种潜在多样性。