PDBsum entry 1u3h

Immune system

PDB id: 1u3h

Contents

Protein chains

110 a.a. *

111 a.a. *

182 a.a. *

189 a.a. *

12 a.a. *

Waters ×183

* Residue conservation analysis

PDB id:

1u3h

Name:

Immune system

Title:

Crystal structure of mouse tcr 172.10 complexed with mhc class ii i-au molecule at 2.4 a

Structure:

T-cell receptor alpha-chain. Chain: a, e. Fragment: v2.3-j39-c. Engineered: yes. Mouse tcrvbeta 172.10, extracellular variable domain. Chain: b, f. Engineered: yes. Mutation: yes. H-2 class ii histocompatibility antigen, a-u alpha chain.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: h2-aa. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell_line: s2.

Biol. unit:

Pentamer (from PQS)

Resolution:

2.42Å R-factor: 0.232 R-free: 0.274

Authors:

J.Maynard,K.Petersson,D.H.Wilson,E.J.Adams,S.E.Blondelle, M.J.Boulanger,D.B.Wilson,K.C.Garcia

Key ref:

J.Maynard et al. (2005). Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity. Immunity, 22, 81-92. PubMed id: 15664161 DOI: 10.1016/j.immuni.2004.11.015

Date:

21-Jul-04 Release date: 17-May-05

Protein chains

Q5R1B3  (Q5R1B3_MOUSE) -  TRAV14-3 (Fragment) from Mus musculus

Seq: 120 a.a.

Struc: 110 a.a.*

Protein chains

P04213  (TVB5_MOUSE) -  T-cell receptor beta chain V region C5 (Fragment) from Mus musculus

Seq: 122 a.a.

Struc: 111 a.a.*

Protein chains

P14438  (HA2U_MOUSE) -  H-2 class II histocompatibility antigen, A-U alpha chain (Fragment) from Mus musculus

Seq: 227 a.a.

Struc: 182 a.a.

Protein chains

P06344  (HB2U_MOUSE) -  H-2 class II histocompatibility antigen, A-U beta chain from Mus musculus

Seq: 263 a.a.

Struc: 189 a.a.

Protein chains

P04370  (MBP_MOUSE) -  Myelin basic protein from Mus musculus

Seq: 250 a.a.

Struc: 12 a.a.*

* PDB and UniProt seqs differ at 26 residue positions (black crosses)

DOI no: 10.1016/j.immuni.2004.11.015

Immunity 22:81-92 (2005)

PubMed id: 15664161

Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity.

J.Maynard, K.Petersson, D.H.Wilson, E.J.Adams, S.E.Blondelle, M.J.Boulanger, D.B.Wilson, K.C.Garcia.

ABSTRACT

T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class II MHC I-Au, recognition of the MHC is dominated by the Vbeta domain of the TCR, which interacts with the MHC alpha chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly prefers the native MBP contact residues. We suggest that while TCR scanning of pMHC may be degenerate due to the TCR germline bias for MHC, recognition of structurally distinct agonist peptides is not indicative of TCR promiscuity, but rather highly specific alternative solutions to TCR engagement.

Selected figure(s)

Figure 1.
Figure 1. Structure of TCR 172.10 in Complex with I-A^u/MBP1-11(A) Ribbon representation of the complex including 172.10Vα (red), 172.10Vβ (blue), I-A^u (green), and MBP residues 1–8 (yellow). The CDR loops from 172.10 are colored as follows: CDR1α (magenta), CDR2α (pink), CDR3α (red), CDR1β (maroon), CDR2β (cyan), and CDR3β (blue).(B) Side view (turned 90° from [A]) of the complex. MBP peptide is shown as a transparent molecular surface (yellow) with ball-and-stick representations of amino acids inside, including the leader peptide (gray). The β1 helix from I-A^u is in the front, and the α1 helix is behind the peptide.(C) 172.10 footprint showing docking orientation on I-A^u/MBP1-11. Peptide-MHC is shown as a green surface (peptide in yellow, leader residues in gray), and the 172.10 CDR loops are drawn as tubes and labeled. This and all subsequent figures were produced with PyMol (Delano, 2002).

Figure 2.
Figure 2. 172.10 Vα and Vβ Interactions with β1 and α1 Helices of I-A^u(A) Overview of the interface between 172.10 Vα (red) and Vβ (blue) and I-A^u (green)/MBP-peptide (yellow).(B) Contact interface between the 172.10 Vα and the I-Au β1 helix. All contacts are van der Waals.(C) Contact interface between the 172.10 Vβ and the I-Au α1 helix showing both hydrogen bonds and van der Waals interactions. Labeled residues are those involved in the hydrogen-bonding network.

The above figures are reprinted by permission from Cell Press: Immunity (2005, 22, 81-92) copyright 2005.

Figures were selected by an automated process.