3CPL

Crystal Structure of H-2Db in complex with a variant M6A of the NP366 peptide from influenza A virus

Summary for 3CPL

• Entry DOI: 10.2210/pdb3cpl/pdb
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, NP366 peptide, ... (4 entities in total)
• Functional Keywords: h-2db, influenza, np366, immunology, glycoprotein, immune response, membrane, mhc i, transmembrane, immunoglobulin domain, polymorphism, secreted, immune system
• Biological source: Mus musculus (Mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01899; Secreted: P01887
• Total number of polymer chains: 6
• Total formula weight: 89321.86

Authors

Kedzierska, K.,Guillonneau, C.,Hatton, L.A.,Stockwell, D.,Gras, S.,Webby, R.,Rossjohn, J.,Purcell, A.W.,Doherty, P.C.,Turner, S.J. (deposition date: 2008-03-31, release date: 2008-11-18, Last modification date: 2024-10-30)

Primary citation

Kedzierska, K.,Guillonneau, C.,Gras, S.,Hatton, L.A.,Webby, R.,Purcell, A.W.,Rossjohn, J.,Doherty, P.C.,Turner, S.J.
Complete modification of TCR specificity and repertoire selection does not perturb a CD8+ T cell immunodominance hierarchy.
Proc.Natl.Acad.Sci.USA, 105:19408-19413, 2008

PubMed Abstract: Understanding T cell immunodominance hierarchies is fundamental to the development of cellular-based vaccines and immunotherapy. A combination of influenza virus infection in C57BL/6J mice and reverse genetics is used here to dissect the role of T cell antigen receptor (TCR) repertoire in the immunodominant D(b)NP(366)CD8(+) T cell response. Infection with an engineered virus (NPM6A) containing a single alanine (A) mutation at the critical p6 NP(366-374) residue induced a noncross-reactive CD8(+) T cell response characterized by a novel, narrower TCR repertoire per individual mouse that was nonetheless equivalent in magnitude to that generated after WT virus challenge. Although of lower overall avidity, the levels of both cytotoxic T lymphocyte activity and cytokine production were comparable with those seen for the native response. Importantly, the overdominance profile characteristic of secondary D(b)NP(366)-specific clonal expansions was retained for the NPM6A mutant. The primary determinants of immunodominance in this endogenous, non-TCR-transgenic model of viral immunity are thus independent of TCR repertoire composition and diversity. These findings both highlight the importance of effective antigen dose for T cell vaccination and/or immunotherapy and demonstrate the feasibility of priming the memory T cell compartment with engineered viruses to protect against commonly selected mutants viral (or tumor) escape mutants.

PubMed: 19047637
DOI: 10.1073/pnas.0810274105

Experimental method

X-RAY DIFFRACTION (2.5 Å)