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
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作者:
KONIG, R
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机构:NIAID, IMMUNOL LAB, LYMPHOCYTE BIOL SECT, BETHESDA, MD 20892 USA
KONIG, R
SHEN, XL
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机构:NIAID, IMMUNOL LAB, LYMPHOCYTE BIOL SECT, BETHESDA, MD 20892 USA
SHEN, XL
GERMAIN, RN
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机构:NIAID, IMMUNOL LAB, LYMPHOCYTE BIOL SECT, BETHESDA, MD 20892 USA
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.