胸腺中T细胞选择的差异亲和力模型的证据。

Evidence for a differential avidity model of T cell selection in the thymus.

作者信息

Ashton-Rickardt P G, Bandeira A, Delaney J R, Van Kaer L, Pircher H P, Zinkernagel R M, Tonegawa S

机构信息

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139.

出版信息

Cell. 1994 Feb 25;76(4):651-63. doi: 10.1016/0092-8674(94)90505-3.

DOI:10.1016/0092-8674(94)90505-3

PMID:8124708

Abstract

Positive and negative selection of a lymphocytic choriomeningitis virus (LCMV) peptide-specific, H-2Db-restricted T cell clone (P14) was studied using TAP1- and TAP1+ mice transgenic for P14 T cell receptor (TCR) alpha and beta genes. Positive selection of transgenic CD8+ P14 cells was impaired in TAP1- mice. Addition of the LCMV peptide to TAP1- fetal thymic organ cultures (FTOCs) at low and high concentrations induced positive and negative selection of CD8+ P14 cells, respectively, while addition of the same peptide to TAP1+ FTOCs induced negative selection even at low concentrations. Both types of selection were peptide specific. Thus, a critical parameter that controls the fate of a thymocyte seems to be the number of TCRs engaged with complexes of peptide and major histocompatibility complex. When this number is low, positive selection occurs, and when it is high, negative selection takes place. These findings support a differential avidity model of T cell selection.

摘要

利用转染了P14 T细胞受体（TCR）α和β基因的TAP1 -和TAP1 +小鼠，研究了淋巴细胞性脉络丛脑膜炎病毒（LCMV）肽特异性、H - 2Db限制性T细胞克隆（P14）的阳性和阴性选择。在TAP1 -小鼠中，转基因CD8 + P14细胞的阳性选择受损。向TAP1 -胎儿胸腺器官培养物（FTOC）中添加低浓度和高浓度的LCMV肽分别诱导了CD8 + P14细胞的阳性和阴性选择，而向TAP1 + FTOC中添加相同的肽即使在低浓度下也诱导了阴性选择。两种类型的选择都是肽特异性的。因此，控制胸腺细胞命运的一个关键参数似乎是与肽和主要组织相容性复合体复合物结合的TCR数量。当这个数量低时，发生阳性选择，当数量高时，发生阴性选择。这些发现支持了T细胞选择的差异亲和力模型。