2ZSV

Crystal structure of H-2Kb in complex with JHMV epitope S598

Summary for 2ZSV

• Entry DOI: 10.2210/pdb2zsv/pdb
• Related: 2ZSW
• Descriptor: H-2 class I histocompatibility antigen, K-B alpha chain, Beta-2-microglobulin, 8-mer peptide from spike glycoprotein, ... (6 entities in total)
• Functional Keywords: ig fold, protein-protein interactions, immune system, subdominant epitope, glycoprotein, immune response, membrane, mhc i, transmembrane, immunoglobulin domain, secreted
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01901; Secreted: P01887
• Total number of polymer chains: 6
• Total formula weight: 90482.60

Authors

Theodossis, A.,Dunstone, M.A.,Rossjohn, J. (deposition date: 2008-09-18, release date: 2008-11-04, Last modification date: 2023-11-15)

Primary citation

Butler, N.S.,Theodossis, A.,Webb, A.I.,Nastovska, R.,Ramarathinam, S.H.,Dunstone, M.A.,Rossjohn, J.,Purcell, A.W.,Perlman, S.
Prevention of cytotoxic T cell escape using a heteroclitic subdominant viral T cell determinant.
Plos Pathog., 4:-, 2008

PubMed Abstract: High affinity antigen-specific T cells play a critical role during protective immune responses. Epitope enhancement can elicit more potent T cell responses and can subsequently lead to a stronger memory pool; however, the molecular basis of such enhancement is unclear. We used the consensus peptide-binding motif for the Major Histocompatibility Complex molecule H-2K(b) to design a heteroclitic version of the mouse hepatitis virus-specific subdominant S598 determinant. We demonstrate that a single amino acid substitution at a secondary anchor residue (Q to Y at position 3) increased the stability of the engineered determinant in complex with H-2K(b). The structural basis for this enhanced stability was associated with local alterations in the pMHC conformation as a result of the Q to Y substitution. Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Collectively, our findings provide a basis for the enhanced immunogenicity of an engineered determinant that will serve as a template for guiding the development of heteroclitic T cell determinants with applications in prevention of CTL escape in chronic viral infections as well as in tumor immunity.

PubMed: 18949029
DOI: 10.1371/journal.ppat.1000186

Experimental method

X-RAY DIFFRACTION (1.8 Å)