PDBsum entry 3cvi

Immune system

PDB id: 3cvi

Contents

Protein chains

213 a.a. *

209 a.a. *

Waters ×437

* Residue conservation analysis

PDB id:

3cvi

Name:

Immune system

Title:

How tcr-like antibody recognizes mhc-bound peptide

Structure:

25-d1.16 heavy chain. Chain: h. 25-d1.16 light chain. Chain: l

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Organism_taxid: 10090

Resolution:

1.80Å R-factor: 0.219 R-free: 0.264

Authors:

T.Mareeva,E.Martinez-Hackert,Y.Sykulev

Key ref:

T.Mareeva et al. (2008). How a T Cell Receptor-like Antibody Recognizes Major Histocompatibility Complex-bound Peptide. J Biol Chem, 283, 29053-29059. PubMed id: 18703505 DOI: 10.1074/jbc.M804996200

Date:

18-Apr-08 Release date: 23-Sep-08

Protein chain

No UniProt id for this chain

Struc: 213 a.a.

Protein chain

No UniProt id for this chain

Struc: 209 a.a.

DOI no: 10.1074/jbc.M804996200

J Biol Chem 283:29053-29059 (2008)

PubMed id: 18703505

How a T Cell Receptor-like Antibody Recognizes Major Histocompatibility Complex-bound Peptide.

T.Mareeva, E.Martinez-Hackert, Y.Sykulev.

ABSTRACT

We determined the crystal structures of the T cell receptor (TCR)-like antibody 25-D1.16 Fab fragment bound to a complex of SIINFEKL peptide from ovalbumin and the H-2K(b) molecule. Remarkably, this antibody directly "reads" the structure of the major histocompatibility complex (MHC)-bound peptide, employing the canonical diagonal binding mode utilized by most TCRs. This is in marked contrast with another TCR-like antibody, Hyb3, bound to melanoma peptide MAGE-A1 in association with HLA-A1 MHC class I. Hyb3 assumes a non-canonical orientation over its cognate peptide-MHC and appears to recognize a conformational epitope in which the MHC contribution is dominant. We conclude that TCR-like antibodies can recognize MHC-bound peptide via two different mechanisms: one is similar to that exploited by the preponderance of TCRs and the other requires a non-canonical antibody orientation over the peptide-MHC complex.

Selected figure(s)

Figure 2.
Positioning of 25-D1.16 and Hyb3 Fab fragments of TCR-like antibodies over cognate pMHC complexes. The left panel shows the 25-D1.16-pOV8-K^b complex, and the right panel shows the MAGE-A1-HLA-A1 complex. Fab heavy and light chains are colored light and dark gray, respectively. The MHC heavy chain and β[2]m are shown in cyan and dark blue, respectively. 25-D1.16 assumes an orientation that is common for TCRs, with the CDR1 and CDR2 loops contacting K^b helices and the CDR3 loops forming direct contacts with the peptide. MAGE-A1-HLA-A1-bound Hyb3 has an atypical orientation, tilting toward helix α[1] without contacting helix α[2] and forming few direct contacts with the peptide.

Figure 5.
Schematic representation of the positioning of 25-D1.16 and Hyb3 antibodies. 25-D1.16 and KB5-C20 TCR (11) utilize a very similar mode of recognition of MHC-bound peptide that is distinct from that used by Hyb3 antibodies (4). Red and green vectors show virtually identical orientations of 25-D1.16 and KB5-C20 TCR; the dark blue vector indicates a profoundly different orientation of Hyb3; and the black vector indicates peptide positioning in the binding groove of both H2-K^b and HLA-A1 MHC-I proteins.

The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2008, 283, 29053-29059) copyright 2008.

Figures were selected by the author.