Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity.
AuthorsHolst J, Wang H, Eder KD, Workman CJ, Boyd KL, Baquet Z, Singh H, Forbes K, Chruscinski A, Smeyne R, van Oers NS, Utz PJ, Vignali DA
JournalNat Immunol
PubMed ID18469818
'The T cell antigen receptor (TCR)-CD3 complex is unique in having ten cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs). The physiological importance of this high TCR ITAM number is unclear. Here we generated 25 groups of mice expressing various combinations of wild-type and mutant ITAMs in TCR-CD3 complexes. Mice with fewer ... More
Crystal structure of a human CD3-epsilon/delta dimer in complex with a UCHT1 single-chain antibody fragment.
AuthorsArnett KL, Harrison SC, Wiley DC
JournalProc Natl Acad Sci U S A
PubMed ID15534202
'The alpha/beta T cell receptor complex transmits signals from MHC/peptide antigens through a set of constitutively associated signaling molecules, including CD3-epsilon/gamma and CD3-epsilon/delta. We report the crystal structure at 1.9-A resolution of a complex between a human CD3-epsilon/delta ectodomain heterodimer and a single-chain fragment of the UCHT1 antibody. CD3-epsilon/delta and ... More
CD3 delta establishes a functional link between the T cell receptor and CD8.
AuthorsDoucey MA, Goffin L, Naeher D, Michielin O, Baumgärtner P, Guillaume P, Palmer E, Luescher IF
JournalJ Biol Chem
PubMed ID12215456
'T cells expressing T cell receptor (TCR) complexes that lack CD3 delta, either due to deletion of the CD3 delta gene, or by replacement of the connecting peptide of the TCR alpha chain, exhibit severely impaired positive selection and TCR-mediated activation of CD8 single-positive T cells. Because the same defects ... More
Stoichiometry of the T-cell receptor-CD3 complex and key intermediates assembled in the endoplasmic reticulum.
AuthorsCall ME, Pyrdol J, Wucherpfennig KW
JournalEMBO J
PubMed ID15152191
'The T-cell receptor (TCR)-CD3 complex is critical for T-cell development and function, and represents one of the most complex transmembrane receptors. Models of different stoichiometry and valency have been proposed based on cellular experiments and these have important implications for the mechanisms of receptor triggering. Since determination of receptor stoichiometry ... More
CD3 deficiencies.
AuthorsFischer A, de Saint Basile G, Le Deist F
JournalCurr Opin Allergy Clin Immunol
PubMed ID16264327
The molecular characterization of inherited T-cell immunodeficiencies has contributed to delineating key factors in human T-cell development. This review reports on the recent description of deleterious mutations in the genes encoding CD3 subunits expressed at the T-lymphocyte membrane in association with the T-cell receptor. ... More
Crystal structure of the human T cell receptor CD3 epsilon gamma heterodimer complexed to the therapeutic mAb OKT3.
The CD3 epsilon gamma heterodimer is essential for expression and function of the T cell receptor. The crystal structure of the human CD3 epsilon gamma heterodimer is described to 2.1-A resolution complexed with OKT3, a therapeutic mAb that not only activates and tolerizes mature T cells but also induces regulatory ... More