Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
30
|
| pubmed:dateCreated |
1996-9-3
|
| pubmed:abstractText |
Binding of viral antigens to major histocompatibility complex (MHC) class I molecules is a critical step in the activation process of CD8(+) cytotoxic T lymphocytes. In this study, we investigated the impact of structural factors at non-anchor residues in peptide-MHC interaction using the model of lymphocytic choriomeningitis virus (LCMV) infection of its natural host, the mouse. Altering viral genes by making reassortants, recombinants, and using synthetic peptides, CD8(+) cytotoxic T lymphocytes were shown to recognize only three H-2Db-restricted epitopes, GP amino acids 33-41/43, GP 276-286, and NP 396-404. However, LCMV NP and GP proteins contain 31 other peptides bearing the H-2Db motif. These 34 LCMV peptides and 11 other known H2-Db-restricted peptides were synthesized and examined for MHC binding properties. Despite the presence of the H-2Db binding motif, the majority of LCMV peptides showed weak or no affinity for H-2Db. We observed that dominant negative structural elements located at non-anchor positions played a crucial role in peptide-MHC interaction. By comparative sequence analysis of strong versus non-binders and using molecular modeling, we delineated these negative elements and evaluated their impact on peptide-MHC interaction. Our findings were validated by showing that a single mutation of a favorable non-anchor residue in the sequence of known viral epitopes for a negative element resulted in dramatic reduction of antigen presentation properties, while conversely, substitution of one negative for a positive element in the sequence of a non-binder conferred to the peptide an ability to now bind to MHC molecules.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
26
|
| pubmed:volume |
271
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
17829-36
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8663374-Amino Acid Sequence,
pubmed-meshheading:8663374-Animals,
pubmed-meshheading:8663374-Antigens, Viral,
pubmed-meshheading:8663374-Computer Simulation,
pubmed-meshheading:8663374-Cytotoxicity, Immunologic,
pubmed-meshheading:8663374-H-2 Antigens,
pubmed-meshheading:8663374-Lymphocytic choriomeningitis virus,
pubmed-meshheading:8663374-Mice,
pubmed-meshheading:8663374-Models, Molecular,
pubmed-meshheading:8663374-Molecular Sequence Data,
pubmed-meshheading:8663374-Oligopeptides,
pubmed-meshheading:8663374-Protein Binding,
pubmed-meshheading:8663374-Structure-Activity Relationship,
pubmed-meshheading:8663374-T-Lymphocytes, Cytotoxic
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Binding of viral antigens to major histocompatibility complex class I H-2Db molecules is controlled by dominant negative elements at peptide non-anchor residues. Implications for peptide selection and presentation.
|
| pubmed:affiliation |
Institut de Pharmacologie et de Biologie Structurale, CNRS, 205 route de Narbonne, 31400 Toulouse, France.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|