Structural Biology of the T-cell Receptor: Insights into Receptor Assembly, Ligand Recognition, and Initiation of Signaling

Abstract

The T-cell receptor (TCR)-CD3 complex serves as a central paradigm for general principles of receptor assembly, ligand recognition, and signaling in the immune system. There is no other receptor system that matches the diversity of both receptor and ligand components. The recent expansion of the immunological structural database is beginning to identify key principles of MHC and peptide recognition. The multicomponent assembly of the TCR complex illustrates general principles used by many receptors in the immune system, which rely on basic and acidic transmembrane residues to guide assembly. The intrinsic binding of the cytoplasmic domains of the CD31 and z chains to the inner leaflet of the plasma membrane represents a novel mechanism for control of receptor activation: Insertion of critical CD31 tyrosines into the hydrophobic membrane core prevents their phosphorylation before receptor engagement. LIGAND BINDING BY THE EXTRACELLULAR DOMAINS OF T-CELL RECEPTORS: STRUCTURAL BASIS OF ab AND gd TCR BINDING TO A DIVERSE GROUP OF LIGANDST he structures of many T-cellreceptors (TCRs) in their ligand-bound state have now been determined, allowing some of the general rules of antigen recognition to be distilled. Though the best studied interaction is the binding of abTCR with peptide-MHC complexes, it is highly instructive to compare the prototypical binding to peptide-MHC with the recognition of lipid antigen-CD1 complexes and engagement of nonclassical MHC class I molecules by gdTCRs. These comparisons show that the recognition strategies for these

Biologically active LIL proteins built with minimal chemical diversity

“…Next we wished to investigate whether the traptamers interacted with the PDGFβR, but the very hydrophobic nature of the traptamers complicates biophysical analysis, which traditionally has been used to study the interaction of natural and artificial transmembrane domains with far greater chemical diversity (10,31,32). Therefore, we used coimmunoprecipitation to determine if the traptamers were present in a stable complex with the PDGFβR in transformed cells.…”

Lipid-dependent conformational dynamics underlie the functional versatility of T-cell receptor

“…R1 and R2 are relaxation rates at which the longitudinal and transverse components of magnetization (Mz and Mxy) return to equilibrium after perturbation, respectively, while { 1 H}-15 N NOE provides information and the motion of individual N-H bond vectors. The { 1 H}- 15 N NOE values showed variations in the range of 0.20-0.71 with an average of 0.48. In general, flexible residues give { 1 H}- 15 N NOE values less than 0.65 ( Figure 4C).…”

“…The { 1 H}- 15 N NOE values showed variations in the range of 0.20-0.71 with an average of 0.48. In general, flexible residues give { 1 H}- 15 N NOE values less than 0.65 ( Figure 4C). Therefore, the lipid-bound CD should be very flexible.…”

“…The transverse relaxation rates of the amide protons ( 1 HN-Γ 2 ) were measured using two time-points method [69]. Peak intensity changes induced by TEMPOL were also measured for the two 1 H- 15 N TROSY spectra at the TEMPOL concentration of 0 mM and 15 mM, respectively.…”

“…A TCR contains four subunits, an antigen-binding TCRαβ subunit and three signaling subunits, CD3εδ, CD3εγ and CD3ζζ [15]. The TCRαβ subunit recognizes antigen on the extracellular side but cannot trigger intracellular signaling because its cytoplasmic domains do not contain signaling motif.…”