3cpl
Crystal Structure of H-2Db in complex with a variant M6A of the NP366 peptide from influenza A virusCrystal Structure of H-2Db in complex with a variant M6A of the NP366 peptide from influenza A virus
Structural highlights
FunctionHA11_MOUSE Involved in the presentation of foreign antigens to the immune system. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedUnderstanding 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. Complete modification of TCR specificity and repertoire selection does not perturb a CD8+ T cell immunodominance hierarchy.,Kedzierska K, Guillonneau C, Gras S, Hatton LA, Webby R, Purcell AW, Rossjohn J, Doherty PC, Turner SJ Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19408-13. Epub 2008 Dec 1. PMID:19047637[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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