共 35 条
Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4+ T cells in vivo
被引:37
作者:
Riberdy, JM
[1
]
Mostaghel, E
[1
]
Doyle, C
[1
]
机构:
[1] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
来源:
关键词:
D O I:
10.1073/pnas.95.8.4493
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
The experiments presented in this report were designed to specifically examine the role of CD4-major histocompatibility complex (MHC) class II interactions during T cell development in vivo. We have generated transgenic mice expressing class II molecules that cannot interact with CD4 but that are otherwise competent to present peptides to the T cell receptor. MHC class II expression was reconstituted in A beta gene knock-out mice by injection of a transgenic construct encoding either the wild-type I-A beta(b) protein or a construct encoding a mutation designed to specifically disrupt binding to the CD4 molecule. We demonstrate that the mutation, EA137 and VA142 in the beta 2 domain of I-A(b), is sufficient to disrupt CD4-MHC class II interactions in vivo. Furthermore, we show that this interaction is critical for the efficient selection of a complete repertoire of mature CD4+ T helper cells as evidenced by drastically reduced numbers of conventional CD4+ T cells in animals expressing the EA137/VA142 mutant I-A(b) and by the failure to positively select the transgenic AND T cell receptor on the mutated I-A(.) These results underscore the importance of the CD4-class II interaction in the development of mature peripheral CD4(+) T cells.
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页码:4493 / 4498
页数:6
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