1RK0

Mhc Class I H-2Kb Heavy Chain Complexed With beta-2 Microglobulin and Herpes Simplex Virus Glycoprotein B peptide

Summary for 1RK0

• Entry DOI: 10.2210/pdb1rk0/pdb
• Descriptor: H-2 class I histocompatibility antigen, K-B alpha chain, Beta-2-microglobulin, Glycoprotein B, ... (5 entities in total)
• Functional Keywords: mhc, class i, virus, tcr, herpes, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 3
• Total formula weight: 44496.93

Authors

Miley, M.J.,Messaoudi, I.,Nikolich-Zugich, J.,Fremont, D.H. (deposition date: 2003-11-20, release date: 2004-12-14, Last modification date: 2024-11-20)

Primary citation

Miley, M.J.,Messaoudi, I.,Metzner, B.M.,Wu, Y.,Nikolich-Zugich, J.,Fremont, D.H.
Structural Basis for the Restoration of TCR Recognition of an MHC Allelic Variant by Peptide Secondary Anchor Substitution
J.Exp.Med., 200:1445-1454, 2004

PubMed Abstract: Major histocompatibility complex (MHC) class I variants H-2K(b) and H-2K(bm8) differ primarily in the B pocket of the peptide-binding groove, which serves to sequester the P2 secondary anchor residue. This polymorphism determines resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell responses to the immunodominant glycoprotein B(498-505) epitope, HSV8. We studied the molecular basis of these effects and confirmed that T cell receptors raised against K(b)-HSV8 cannot recognize H-2K(bm8)-HSV8. However, substitution of Ser(P2) to Glu(P2) (peptide H2E) reversed T cell receptor (TCR) recognition; H-2K(bm8)-H2E was recognized whereas H-2K(b)-H2E was not. Insight into the structural basis of this discrimination was obtained by determining the crystal structures of all four MHC class I molecules in complex with bound peptide (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can explain the differential TCR recognition. However, a correlation is apparent between the recognition data and the underlying peptide-binding groove chemistry of the B pocket, revealing that secondary anchor residues can profoundly affect TCR engagement through mechanisms distinct from the alteration of the resting state conformation of the pMHC surface.

PubMed: 15557346
DOI: 10.1084/jem.20040217

Experimental method

X-RAY DIFFRACTION (2.61 Å)