PDBsum entry 4p46

Immune system

PDB id: 4p46

Contents

Protein chains

179 a.a.

200 a.a.

199 a.a.

238 a.a.

PDB id:

4p46

Name:

Immune system

Title:

J809.B5 y31a tcr bound to iab3k

Structure:

H-2 class ii histocompatibility antigen, a-b alpha chain. Chain: c. Fragment: residues 27-205. Synonym: iaalpha. Engineered: yes. 3k peptide,h-2 class ii histocompatibility antigen, a beta chain. Chain: d. Fragment: residues 30-218.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: h2-aa. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic construct, mus musculus. Organism_taxid: 32630, 10090. Gene: h2-ab1, h2-iabeta.

Resolution:

2.85Å R-factor: 0.185 R-free: 0.247

Authors:

B.D.Stadinski,E.S.Huseby,P.Trenh,L.J.Stern

Key ref:

B.D.Stadinski et al. (2014). Effect of CDR3 sequences and distal V gene residues in regulating TCR-MHC contacts and ligand specificity. J Immunol, 192, 6071-6082. PubMed id: 24813203 DOI: 10.4049/jimmunol.1303209

Date:

11-Mar-14 Release date: 28-May-14

Protein chain

P14434  (HA2B_MOUSE) -  H-2 class II histocompatibility antigen, A-B alpha chain from Mus musculus

Seq: 256 a.a.

Struc: 179 a.a.

Protein chain

P14483  (HB2A_MOUSE) -  H-2 class II histocompatibility antigen, A beta chain from Mus musculus

Seq: 265 a.a.

Struc: 200 a.a.*

Protein chain

No UniProt id for this chain

Struc: 199 a.a.

Protein chain

P01850  (TRBC1_HUMAN) -  T cell receptor beta constant 1 from Homo sapiens

Seq: 176 a.a.

Struc: 238 a.a.*

* PDB and UniProt seqs differ at 18 residue positions (black crosses)

DOI no: 10.4049/jimmunol.1303209

J Immunol 192:6071-6082 (2014)

PubMed id: 24813203

Effect of CDR3 sequences and distal V gene residues in regulating TCR-MHC contacts and ligand specificity.

B.D.Stadinski, P.Trenh, B.Duke, P.G.Huseby, G.Li, L.J.Stern, E.S.Huseby.

ABSTRACT

The mature T cell repertoire has the ability to orchestrate immunity to a wide range of potential pathogen challenges. This ability stems from thymic development producing individual T cell clonotypes that express TCRs with unique patterns of Ag reactivity. The Ag specificity of TCRs is created from the combinatorial pairing of one of a set of germline encoded TCR Vα and Vβ gene segments with randomly created CDR3 sequences. How the amalgamation of germline encoded and randomly created TCR sequences results in Ag receptors with unique patterns of ligand specificity is not fully understood. Using cellular, biophysical, and structural analyses, we show that CDR3α residues can modulate the geometry in which TCRs bind peptide-MHC (pMHC), governing whether and how germline encoded TCR Vα and Vβ residues interact with MHC. In addition, a CDR1α residue that is positioned distal to the TCR-pMHC binding interface is shown to contribute to the peptide specificity of T cells. These findings demonstrate that the specificity of individual T cell clonotypes arises not only from TCR residues that create direct contacts with the pMHC, but also from a collection of indirect effects that modulate how TCR residues are used to bind pMHC.