PDBsum entry 2e7l

Immune system

PDB id: 2e7l

Contents

Protein chains

112 a.a. *

112 a.a. *

175 a.a. *

Ligands

GLN-LEU-SER-PRO-PHE-PRO-PHE-ASP-LEU ×2

Waters ×173

* Residue conservation analysis

PDB id:

2e7l

Name:

Immune system

Title:

Structure of a high-affinity mutant of the 2c tcr in complex with ld/ql9

Structure:

Cytotoxic tcell receptor. Chain: a, b. Fragment: unp residues 21-132. Synonym: v alpha, t cell receptor alpha chain. Engineered: yes. Beta-chain. Chain: c, d. Fragment: unp residues 30-144. Synonym: v beta, t cell receptor beta chain.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes. Other_details: synthetic peptide

Resolution:

2.50Å R-factor: 0.225 R-free: 0.246

Authors:

K.C.Garcia,L.A.Colf

Key ref:

L.A.Colf et al. (2007). How a single T cell receptor recognizes both self and foreign MHC. Cell, 129, 135-146. PubMed id: 17418792 DOI: 10.1016/j.cell.2007.01.048

Date:

11-Jan-07 Release date: 24-Apr-07

Protein chains

A2NTU7  (A2NTU7_MOUSE) -  Cytotoxic Tcell receptor from Mus musculus

Seq: 268 a.a.

Struc: 112 a.a.*

Protein chains

A2NTY6  (A2NTY6_MOUSE) -  Beta-chain (Fragment) from Mus musculus

Seq: 144 a.a.

Struc: 112 a.a.*

Protein chains

P01897  (HA1L_MOUSE) -  H-2 class I histocompatibility antigen, L-D alpha chain from Mus musculus

Seq: 362 a.a.

Struc: 175 a.a.*

* PDB and UniProt seqs differ at 22 residue positions (black crosses)

DOI no: 10.1016/j.cell.2007.01.048

Cell 129:135-146 (2007)

PubMed id: 17418792

How a single T cell receptor recognizes both self and foreign MHC.

L.A.Colf, A.J.Bankovich, N.A.Hanick, N.A.Bowerman, L.L.Jones, D.M.Kranz, K.C.Garcia.

ABSTRACT

alphabeta T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 A structure of the 2C TCR complexed with its foreign ligand H-2L(d)-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2K(b)-dEV8. 2C engages both shared and polymorphic residues on L(d) and K(b), as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the L(d)-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2L(d)-QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3alpha interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.

Selected figure(s)

Figure 3.
Figure 3. 2C TCR Interactions with the QL9 Peptide
(A) Closeup view of the 2C/QL9 interface, with QL9 shown as yellow sticks. The CDRα and CDRβ loops of 2C are shown (α pink, β cyan) as tubes with sticks and selected residues are labeled. Hydrogen bonds are drawn as dashes.
(B) Same view as (A), except between 2C and the dEV8 peptide.
(C) The isolated QL9 (green) and dEV8 (brown) are shown from the MHC superposition to appreciate the relatively different peptide structures seen by 2C.
(D) Contact map between 2C CDR3s and QL9 and dEV8 peptides, similar to contact map shown in Figures 2C and 2D. 2C CDR3 residues that only contact dEV8 are shown in brown, and QL9 contacts are in green. 2C residues that contact both dEV8 and QL9 are shown in yellow. Solid lines are vdw and dashed lines are hydrogen bonds.

Figure 6.
Figure 6. 2C TCR Forms Limited Contacts with Shared Amino Acids on L^d and K^b Recognition Surfaces
(A) Molecular surfaces of L^d-QL9 (left) and K^b-dEV8 (right). Shared residues on the MHC helices are drawn in red.
(B) Only a small subset of the total shared residues shown in (A) are also used as direct contacts with 2C in both complexes.
(C) Of the shared MHC contacts shown in (B), only four also contact the same 2C residue in both complexes.
(D) The common TCR-MHC contacts in (C) are structurally and chemically distinct interactions. Shown are the allogeneic and syngeneic complexes superimposed on the MHC. Three common CDR2β and CDR3α contacts (highlighted in C) are significantly perturbed in each complex such that the bond distances and geometries of the interatomic contacts are different, mainly due to the rotational shift of the CDRs along the MHC helix.

The above figures are reprinted by permission from Cell Press: Cell (2007, 129, 135-146) copyright 2007.

Figures were selected by an automated process.