FCCC LOGO Faculty Publications
La Gruta NL , Liu HY , Dilioglou S , Rhodes M , Wiest DL , Vignali DAA
Architectural changes in the TCR : CD3 complex induced by MHC : peptide ligation
Journal of Immunology. 2004 Mar;172(6) :3662-3669
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A hallmark of T cell activation is the ligation-induced down-modulation of the TCR:CD3 complex. However, little is known about the molecular events that drive this process. The CD3 zeta-chain has been shown to play a unique role in regulating the assembly, transport, and cell surface expression of the TCR:CD3 complex. In this study we have investigated the relationship between CD3 and the TCRalphabetaCD3epsilondeltagamma complex after ligation by MHC:peptide complexes. Our results show that there is a significant increase in free surface CD3zeta which is not associated with the TCR:CD3 complex, after T cell stimulation. This may reflect dissociation of CD3zeta from the TCRalphabetaCD3epsilondeltagamma complex or transport of intracellular CD3 directly to the cell surface. We also show that MHC:peptide ligation also results in exposure of the TCR-associated CD3zeta NH2 terminus, which is ordinarily buried in the complex. These observations appears to be dependent on Src famil! y protein tyrosine kinases, which are known to be critical for efficient T cell activation. These data suggest a mechanism by which ligated TCR may be differentiated from unligated TCR and selectively down-modulated.
English Article Life Sciences (LS) Vignali, DAA; St Jude Childrens Hosp, Dept Immunol, 332 N Lauderdale, Memphis, TN 38105 USA. 0022-1767