INVOLVEMENT OF BOTH MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ALPHA-CHAINS AND BETA-CHAINS IN CD4 FUNCTION INDICATES A ROLE FOR ORDERED OLIGOMERIZATION IN T-CELL ACTIVATION

被引:108
作者
KONIG, R
SHEN, XL
GERMAIN, RN
机构
[1] NIAID, IMMUNOL LAB, LYMPHOCYTE BIOL SECT, BETHESDA, MD 20892 USA
[2] UNIV TEXAS, MED BRANCH, SEALY CTR MOLEC SCI, GALVESTON, TX 77555 USA
[3] UNIV TEXAS, MED BRANCH, DEPT MICROBIOL & IMMUNOL, GALVESTON, TX 77555 USA
关键词
D O I
10.1084/jem.182.3.779
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD4 is a membrane glycoprotein on T lymphocytes that binds to the same peptide:major histocompatibility complex (MHC) class II molecule recognized by the antigen-specific receptor (TCR), thereby stabilizing interactions between the TCR and peptide:MHC class II complexes and promoting the localization of the src family tyrosine kinase p56(lck) into the receptor complex. Previous studies identified a solvent-exposed loop on the class II beta 2 domain necessary for binding to CD4 and for eliciting CD4 coreceptor activity. Here, we demonstrate that a second surface-exposed segment of class II is also critical for CD4 function. This site is in the alpha 2 domain, positioned in single class II heterodimers in such a way that it cannot simultaneously interact with the same CD4 molecule as the beta 2 site. The ability of mutations at either site to diminish CD4 function therefore indicates that specifically organized CD4 and/or MHC class II oligomers play a critical role in coreceptor-dependent T cell activation.
引用
收藏
页码:779 / 787
页数:9
相关论文
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