THE MHC CLASS I-RESTRICTED T-CELL RESPONSE TO SENDAI VIRUS-INFECTION IN C57BL/6 MICE - A SINGLE IMMUNODOMINANT EPITOPE ELICITS AN EXTREMELY DIVERSE REPERTOIRE OF T-CELLS
THE MHC CLASS I-RESTRICTED T-CELL RESPONSE TO SENDAI VIRUS-INFECTION IN C57BL/6 MICE - A SINGLE IMMUNODOMINANT EPITOPE ELICITS AN EXTREMELY DIVERSE REPERTOIRE OF T-CELLS
复制标题
DOI：
10.1093/intimm/6.11.1767
复制
发表时间：
1994-11-01
影响因子：
4.4
通讯作者：
WOODLAND, DL
中科院分区：
文献类型：
--
作者：
COLE, GA;HOGG, TL;WOODLAND, DL
我们使用仙台病毒感染C57BL/6小鼠作为模型来研究T细胞对单一主要组织相容性复合体（MHC）I类表位的应答。从病毒感染小鼠的支气管肺泡灌洗液中获取的细胞，以及在体外对来自纵隔淋巴结的细胞进行再刺激后，对单一核蛋白表位NP324 - 332/K - b具有强烈的细胞毒性。为了将T细胞受体（TCR）的使用与对免疫优势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液和纵隔淋巴结细胞中产生了T细胞杂交瘤。总共鉴定出20个杂交瘤，它们在受到NP324 - 332脉冲的L929 - K - b细胞刺激时特异性地分泌白细胞介素 - 2（IL - 2）。这组杂交瘤中TCR的使用极其多样化。C57BL/6小鼠品系中超过一半的可用Jβ和V - β元件在杂交瘤中有所体现。同样，V - α的使用也是多样的，所测序的12条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链连接区存在一个精氨酸残基。这些数据表明，多样化的TCR库能够识别单一的MHC I类表位。此外，数据表明小鼠在对自然病毒感染的初次应答中利用了这种潜在的多样性。
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/K-b. 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-K-b 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.