Alteration at a single amino acid residue in the T cell receptor alpha chain complementarity determining region 2 changes the differentiation of naive CD4 T cells in response to antigen from T helper cell type 1 (Th1) to Th2.
Alteration at a single amino acid residue in the T cell receptor alpha chain complementarity determining region 2 changes the differentiation of naive CD4 T cells in response to antigen from T helper cell type 1 (Th1) to Th2.
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DOI：
10.1084/jem.191.12.2065
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发表时间：
2000-06-19
期刊：
影响因子：
--
通讯作者：
Janeway CA Jr
中科院分区：
文献类型：
--
作者：
Blander JM;Sant'Angelo DB;Bottomly K;Janeway CA Jr
为了研究T细胞受体（TCR）在单个与肽接触的残基处的结构变化是否会影响抗原肽对T细胞的启动，我们制作了在D10.G4.1（D10）TCR的TCRα链上有一个点突变的转基因小鼠，并将它们与D10β链转基因小鼠进行繁殖。该突变是在第51位由亮氨酸替换为丝氨酸（L51S），我们已经确定这个位置与肽的第二个氨基酸接触，使得对参照肽的反应降低了约100倍。参照肽CA134 - 146（CA - WT）在肽位置2的精氨酸突变为甘氨酸（R2G）后，对这种改变的TCR恢复了完全反应。当我们在体外检测初始CD4 T细胞的启动时，我们观察到，在来自D10 TCR转基因小鼠的初始CD4 T细胞中能诱导1型辅助性T细胞（Th1）反应的CA - WT剂量，在来自L51S的初始CD4 T细胞中仅产生Th2反应。然而，当我们用R2G肽启动相同的T细胞时，我们在D10和L51S的初始CD4 T细胞中都观察到了Th1启动。我们从这些数据得出结论，TCR在一个与主要组织相容性复合体结合肽接触的关键位置发生突变，与T细胞分化从Th1向Th2的转变有关。
To study whether changes in the structure of a T cell receptor (TCR) at a single peptide-contacting residue could affect T cell priming with antigenic peptide, we made transgenic mice with a point mutation in the TCR α chain of the D10.G4.1 (D10) TCR and bred them to D10 β chain transgenic mice. The mutation consisted of a leucine to serine substitution at position 51 (L51S), which we had already established contacted the second amino acid of the peptide such that the response to the reference peptide was reduced by ∼100-fold. A mutation in the reference peptide CA134–146 (CA-WT) from the arginine at peptide position 2 to glycine (R2G) restored full response to this altered TCR. When we examined in vitro priming of naive CD4 T cells, we observed that the response to doses of CA-WT that induced T helper cell type 1 (Th1) responses in naive CD4 T cells from mice transgenic for the D10 TCR gave only Th2 responses in naive CD4 T cells derived from the L51S. However, when we primed the same T cells with the R2G peptide, we observed Th1 priming in both D10 and L51S naive CD4 T cells. We conclude from these data that a mutation in the TCR at a key position that contacts major histocompatibility complex–bound peptide is associated with a shift in T cell differentiation from Th1 to Th2.
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DOI：
10.1084/jem.182.5.1591
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Constant S;Pfeiffer C;Woodard A;Pasqualini T;Bottomly K
通讯作者：
Bottomly K
影响因子：
32.4
作者：
LUESCHER, IF;ANJUERE, F;ROMERO, P
通讯作者：
ROMERO, P
影响因子：
56.9
作者：
Fearon, DT;Locksley, RM
通讯作者：
Locksley, RM
影响因子：
56.9
作者：
EVAVOLD, BD;ALLEN, PM
通讯作者：
ALLEN, PM
影响因子：
64.8
作者：
JORGENSEN, JL;ESSER, U;DAVIS, MM
通讯作者：
DAVIS, MM