1FG2

CRYSTAL STRUCTURE OF THE LCMV PEPTIDIC EPITOPE GP33 IN COMPLEX WITH THE MURINE CLASS I MHC MOLECULE H-2DB

Summary for 1FG2

• Entry DOI: 10.2210/pdb1fg2/pdb
• Descriptor: H-2 CLASS I HISTOCOMPATIBILITY ANTIGEN, D-B ALPHA CHAIN, BETA-2 MICROGLOBULIN, LCMV PEPTIDIC EPITOPE GP33, ... (4 entities in total)
• Functional Keywords: ig fold, immune system
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01899; Secreted: P01887
• Total number of polymer chains: 12
• Total formula weight: 181816.14

Authors

Tissot, A.C.,Ciatto, C.,Mittl, P.R.E.,Gruetter, M.G.,Plueckthun, A. (deposition date: 2000-07-27, release date: 2000-10-04, Last modification date: 2024-10-30)

Primary citation

Tissot, A.C.,Ciatto, C.,Mittl, P.R.,Grutter, M.G.,Pluckthun, A.
Viral escape at the molecular level explained by quantitative T-cell receptor/peptide/MHC interactions and the crystal structure of a peptide/MHC complex.
J.Mol.Biol., 302:873-885, 2000

PubMed Abstract: Viral escape, first characterized for the lymphocytic choriomeningitis virus (LCMV) in a mouse transgenic for the P14 T cell-receptor (TCR), can be due to mutations in T-cell epitopes. We have measured the affinity between the H-2D(b) containing the wild-type and two of its "viral escape" epitopes, as well as other altered peptide ligands (APL), by using BIACORE analysis, and solved the crystal structure of H-2D(b) in complex with the wild-type peptide at 2.75 A resolution. We show that viral escape is due to a 50 to 100-fold reduction in the level of affinity between the P14 TCR and the binary complexes of the MHC molecule with the different peptides. Structurally, one of the mutations alters a TCR contact residue, while the effect of the other on the binding of the TCR must be indirect through structural rearrangements. The former is a null ligand, while the latter still leads to some central tolerance. This work defines the structural and energetic threshold for viral escape.

PubMed: 10993729
DOI: 10.1006/jmbi.2000.4501

Experimental method

X-RAY DIFFRACTION (2.754 Å)