Involvement of both major histocompatibility complex class II α and β chains in CD4 function indicates a role for ordered oligomerization in T cell activation

Rolf König, Xiaoli Shen, Ronald N. Germain

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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 β2 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 α2 domain, positioned in single class II heterodimers in such a way that it cannot simultaneously interact with the same CD4 molecule as the β2 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.

Original languageEnglish (US)
Pages (from-to)779-787
Number of pages9
JournalJournal of Experimental Medicine
Volume182
Issue number3
DOIs
StatePublished - Sep 1 1995

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Major Histocompatibility Complex
T-Lymphocytes
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
CD4 Antigens
Peptides
Antigen Receptors
src-Family Kinases
Membrane Glycoproteins
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Involvement of both major histocompatibility complex class II α and β chains in CD4 function indicates a role for ordered oligomerization in T cell activation. / König, Rolf; Shen, Xiaoli; Germain, Ronald N.

In: Journal of Experimental Medicine, Vol. 182, No. 3, 01.09.1995, p. 779-787.

Research output: Contribution to journalArticle

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