About: Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant
Creator	Butler, N Nastovska, R Ramarathinam, S Theodossis, A Webb, A
Source	PMC
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.
has issue date	2008-10-24(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1000186
bibo:pmid	18949029
has license	cc-by
sha1sum (hex)	daffb9a10450c4d9217cf3819a559c31cd49970c
schema:url	https://doi.org/10.1371/journal.ppat.1000186
resource representing a document's title	Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant
has PubMed Central identifier	PMC2563037
has PubMed identifier	18949029
schema:publication	PLoS Pathog
resource representing a document's body	covid:daffb9a10450c4d9217cf3819a559c31cd49970c#body_text
is schema:about of	named entity 'engineered' named entity 'molecular' named entity 'heteroclitic' named entity 'determinants' named entity 'virus-specific' named entity 'avidity' named entity 'epitope' named entity 'Viral' named entity 'T CELL' named entity 'SUBSTITUTION' named entity 'ENGINEERED' named entity 'COMPLEX' named entity 'BASIS' named entity 'IMMUNOGENICITY' named entity 'WILDTYPE' named entity 'VIRUS' named entity 'STABILITY' named entity 'ELICIT' named entity 'INFECTED' named entity 'MUTATED' named entity 'ENCODING' named entity 'LOCAL' named entity 'POOL' named entity 'DEVELOPMENT' named entity 'SELECTION' named entity 'SECOND' named entity 'AS A RESULT OF' named entity 'PMHC' named entity 'USED' named entity 'AVIDITY' named entity 'SECONDARY' named entity 'ENHANCEMENT' named entity 'TUMOR IMMUNITY' named entity 'ANTIGEN' named entity 'DISEASE PROGRESSION' named entity 'AFFINITY' named entity 'ANCHOR' named entity 'PRIMED' named entity 'TEMPLATE' named entity 'CRITICAL' named entity 'ASSOCIATED WITH' named entity 'T CELLS' named entity 'EPITOPE' named entity 'OUR' named entity 'RESIDUE' named entity 'INCREASED' named entity 'CONFORMATION' named entity 'VERSION' named entity 'SERVE' named entity 'DESIGN' named entity 'VIRAL INFECTIONS' named entity 'CONSENSUS' named entity 'ENHANCED' covid:arg/daffb9a10450c4d9217cf3819a559c31cd49970c named entity 'PREVENTION OF' named entity 'SPECIFIC' named entity 'PROVIDE' named entity 'ESCAPE' named entity 'GUIDING' named entity 'PEPTIDE-BINDING' named entity 'VIRAL' named entity 'DETERMINANT' named entity 'ESCAPE' named entity 'POSITION' named entity 'VIRUSES' named entity 'ROLE' named entity 'PERSISTENTLY' named entity 'SINGLE' named entity 'MOUSE HEPATITIS VIRUS' named entity 'RECOMBINANT' named entity 'MEMORY' named entity 'CHRONIC' named entity 'T CELL' named entity 'ALTERATIONS' named entity 'MOLECULAR BASIS' named entity 'DETERMINANTS' named entity 'MICE'

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