1T0N

Conformational switch in polymorphic H-2K molecules containing an HSV peptide

Summary for 1T0N

• Entry DOI: 10.2210/pdb1t0n/pdb
• Related: 1T0M
• Descriptor: H-2 class I histocompatibility antigen, K-B alpha chain, Beta-2-microglobulin, Glycoprotein B, ... (4 entities in total)
• Functional Keywords: immunoglobulin domain, mhc class i alpha domains, hsv peptide, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 6
• Total formula weight: 89238.25

Authors

Webb, A.I.,Borg, N.A.,Dunstone, M.A.,Kjer-Nielsen, L.,Beddoe, T.,McCluskey, J.,Carbone, F.R.,Bottomley, S.P.,Purcell, A.W.,Rossjohn, J. (deposition date: 2004-04-12, release date: 2004-11-23, Last modification date: 2024-10-30)

Primary citation

Webb, A.I.,Borg, N.A.,Dunstone, M.A.,Kjer-Nielsen, L.,Beddoe, T.,McCluskey, J.,Carbone, F.R.,Bottomley, S.P.,Aguilar, M.I.,Purcell, A.W.,Rossjohn, J.
The structure of H-2K(b) and K(bm8) complexed to a herpes simplex virus determinant: evidence for a conformational switch that governs T cell repertoire selection and viral resistance.
J Immunol., 173:402-409, 2004

PubMed Abstract: Polymorphism within the MHC not only affects peptide specificity but also has a critical influence on the T cell repertoire; for example, the CD8 T cell response toward an immunodominant HSV glycoprotein B peptide is more diverse and of higher avidity in H-2(bm8) compared with H-2(b) mice. We have examined the basis for the selection of these distinct antiviral T cell repertoires by comparing the high-resolution structures of K(b) and K(bm8), in complex with cognate peptide Ag. Although K(b) and K(bm8) differ by four residues within the Ag-binding cleft, the most striking difference in the two structures was the disparate conformation adopted by the shared residue, Arg(62). The altered dynamics of Arg(62), coupled with a small rigid-body movement in the alpha(1) helix encompassing this residue, correlated with biased Valpha usage in the B6 mice. Moreover, an analysis of all known TCR/MHC complexes reveals that Arg(62) invariably interacts with the TCR CDR1alpha loop. Accordingly, Arg(62) appears to function as a conformational switch that may govern T cell selection and protective immunity.

PubMed: 15210799
DOI: 10.4049/jimmunol.173.1.402

Experimental method

X-RAY DIFFRACTION (1.8 Å)