Journal ArticleDOI
An αβ T cell receptor structure at 2.5 Å and its orientation in the TCR-MHC complex
K. Christopher Garcia,Massimo Degano,Robyn L. Stanfield,Anders Brunmark,Michael R. Jackson,Per A. Peterson,Luc Teyton,Ian A. Wilson +7 more
TLDR
In this article, the x-ray structure of the complete extracellular fragment of a glycosylated αβ T cell receptor (TCR) was determined at 2.5 angstroms, and its orientation bound to a class I MHC-peptide (pMHC) complex was elucidated from crystals of the TCR- pMHC complex.Abstract:
The central event in the cellular immune response to invading microorganisms is the specific recognition of foreign peptides bound to major histocompatibility complex (MHC) molecules by the αβ T cell receptor (TCR). The x-ray structure of the complete extracellular fragment of a glycosylated αβ TCR was determined at 2.5 angstroms, and its orientation bound to a class I MHC-peptide (pMHC) complex was elucidated from crystals of the TCR-pMHC complex. The TCR resembles an antibody in the variable Vα and Vβ domains but deviates in the constant Cα domain and in the interdomain pairing of Cα with Cβ. Four of seven possible asparagine-linked glycosylation sites have ordered carbohydrate moieties, one of which lies in the Cα-Cβ interface. The TCR combining site is relatively flat except for a deep hydrophobic cavity between the hypervariable CDR3s (complementarity-determining regions) of the α and β chains. The 2C TCR covers the class I MHC H-2K b binding groove so that the Vα CDRs 1 and 2 are positioned over the amino-terminal region of the bound dEV8 peptide, the Vβ chain CDRs 1 and 2 are over the carboxyl-terminal region of the peptide, and the Vα and Vβ CDR3s straddle the peptide between the helices around the central position of the peptide.read more
Citations
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Journal ArticleDOI
Glycosylation and the immune system
TL;DR: Almost all of the key molecules involved in the innate and adaptive immune response are glycoproteins, and specific glycoforms are involved in recognition events.
Journal ArticleDOI
Structure of the complex between human T-cell receptor, viral peptide and HLA-A2
David N. Garboczi,Partho Ghosh,Ursula Utz,Qing R. Fan,William E. Biddison,Don C. Wiley,Don C. Wiley +6 more
TL;DR: The TCP fits diagonally across the MHC peptide-binding site in a surface feature common to all class I and class II MHC molecules, providing evidence that the nature of binding is general.
Journal ArticleDOI
Antibody Recognition of a Highly Conserved Influenza Virus Epitope
Damian C. Ekiert,Gira Bhabha,Marc-André Elsliger,Robert H. E. Friesen,Mandy Jongeneelen,Mark Throsby,Jaap Goudsmit,Ian A. Wilson +7 more
TL;DR: TheCR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.
Journal ArticleDOI
How TCRs Bind MHCs, Peptides, and Coreceptors
TL;DR: The structural basis for MHC restriction and signaling remains elusive as no structural features that define a common binding mode or signaling mechanism have yet been gleaned from the current set of TCR/pMHC complexes.
Journal ArticleDOI
[gamma][delta] cells: a right time and a right place for a conserved third way of protection.
TL;DR: The properties of g Mohammadelta cells form a basis for understanding gammadelta cell interactions with antigens and other cells that in turn form a based for understanding immunoprotective and regulatory functions of gammad delta cells in vivo.
References
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Journal ArticleDOI
Protein structure comparison by alignment of distance matrices
Liisa Holm,Chris Sander +1 more
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Journal ArticleDOI
Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1
Jerry H. Brown,Theodore S. Jardetzky,Joan C. Gorga,Joan C. Gorga,Lawrence J. Stern,Lawrence J. Stern,Robert G. Urban,Jack L. Strominger,Don C. Wiley,Don C. Wiley +9 more
TL;DR: A dimer of the class II αβ heterodimers is seen in the crystal forms of HLA-DR1, suggesting class II HLA dimerization as a mechanism for initiating the cytoplasmic signalling events in T-cell activation.
Journal ArticleDOI
Conformations of immunoglobulin hypervariable regions.
Cyrus Chothia,Cyrus Chothia,Arthur M. Lesk,Anna Tramontano,Michael Levitt,Michael Levitt,Sandra J. Smith-Gill,Gillian M. Air,Steven Sheriff,Steven Sheriff,Eduardo A. Padlan,David R. Davies,W.R. Tulip,Peter M. Colman,Silvia Spinelli,Pedro M. Alzari,Roberto J. Poljak +16 more
TL;DR: There is a small repertoire of main-chain conformations for at least five of the six hypervariable regions of antibodies, and that the particular conformation adopted is determined by a few key conserved residues.