KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif.
Molecular interactions between killer immunoglobulin-like receptors (KIRs) and their MHC class I ligands play a central role in the regulation of natural killer (NK) cell responses to viral pathogens and tumors. Here we identify Mamu-A1*00201 (Mamu-A*02), a common MHC class I molecule in the rhesus...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2011
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/9c08f1e1496f4f9981d0ba1da7d7aa98 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:9c08f1e1496f4f9981d0ba1da7d7aa98 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:9c08f1e1496f4f9981d0ba1da7d7aa982021-11-18T06:03:32ZKIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif.1553-73661553-737410.1371/journal.ppat.1001316https://doaj.org/article/9c08f1e1496f4f9981d0ba1da7d7aa982011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423672/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Molecular interactions between killer immunoglobulin-like receptors (KIRs) and their MHC class I ligands play a central role in the regulation of natural killer (NK) cell responses to viral pathogens and tumors. Here we identify Mamu-A1*00201 (Mamu-A*02), a common MHC class I molecule in the rhesus macaque with a canonical Bw6 motif, as a ligand for Mamu-KIR3DL05. Mamu-A1*00201 tetramers folded with certain SIV peptides, but not others, directly stained primary NK cells and Jurkat cells expressing multiple allotypes of Mamu-KIR3DL05. Differences in binding avidity were associated with polymorphisms in the D0 and D1 domains of Mamu-KIR3DL05, whereas differences in peptide-selectivity mapped to the D1 domain. The reciprocal exchange of the third predicted MHC class I-contact loop of the D1 domain switched the specificity of two Mamu-KIR3DL05 allotypes for different Mamu-A1*00201-peptide complexes. Consistent with the function of an inhibitory KIR, incubation of lymphocytes from Mamu-KIR3DL05(+) macaques with target cells expressing Mamu-A1*00201 suppressed the degranulation of tetramer-positive NK cells. These observations reveal a previously unappreciated role for D1 polymorphisms in determining the selectivity of KIRs for MHC class I-bound peptides, and identify the first functional KIR-MHC class I interaction in the rhesus macaque. The modulation of KIR-MHC class I interactions by viral peptides has important implications to pathogenesis, since it suggests that the immunodeficiency viruses, and potentially other types of viruses and tumors, may acquire changes in epitopes that increase the affinity of certain MHC class I ligands for inhibitory KIRs to prevent the activation of specific NK cell subsets.Arnaud D ColantonioBenjamin N BimberWilliam J NeidermyerR Keith ReevesGalit AlterMarcus AltfeldR Paul JohnsonMary CarringtonDavid H O'ConnorDavid T EvansPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 3, p e1001316 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Arnaud D Colantonio Benjamin N Bimber William J Neidermyer R Keith Reeves Galit Alter Marcus Altfeld R Paul Johnson Mary Carrington David H O'Connor David T Evans KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif. |
| description |
Molecular interactions between killer immunoglobulin-like receptors (KIRs) and their MHC class I ligands play a central role in the regulation of natural killer (NK) cell responses to viral pathogens and tumors. Here we identify Mamu-A1*00201 (Mamu-A*02), a common MHC class I molecule in the rhesus macaque with a canonical Bw6 motif, as a ligand for Mamu-KIR3DL05. Mamu-A1*00201 tetramers folded with certain SIV peptides, but not others, directly stained primary NK cells and Jurkat cells expressing multiple allotypes of Mamu-KIR3DL05. Differences in binding avidity were associated with polymorphisms in the D0 and D1 domains of Mamu-KIR3DL05, whereas differences in peptide-selectivity mapped to the D1 domain. The reciprocal exchange of the third predicted MHC class I-contact loop of the D1 domain switched the specificity of two Mamu-KIR3DL05 allotypes for different Mamu-A1*00201-peptide complexes. Consistent with the function of an inhibitory KIR, incubation of lymphocytes from Mamu-KIR3DL05(+) macaques with target cells expressing Mamu-A1*00201 suppressed the degranulation of tetramer-positive NK cells. These observations reveal a previously unappreciated role for D1 polymorphisms in determining the selectivity of KIRs for MHC class I-bound peptides, and identify the first functional KIR-MHC class I interaction in the rhesus macaque. The modulation of KIR-MHC class I interactions by viral peptides has important implications to pathogenesis, since it suggests that the immunodeficiency viruses, and potentially other types of viruses and tumors, may acquire changes in epitopes that increase the affinity of certain MHC class I ligands for inhibitory KIRs to prevent the activation of specific NK cell subsets. |
| format |
article |
| author |
Arnaud D Colantonio Benjamin N Bimber William J Neidermyer R Keith Reeves Galit Alter Marcus Altfeld R Paul Johnson Mary Carrington David H O'Connor David T Evans |
| author_facet |
Arnaud D Colantonio Benjamin N Bimber William J Neidermyer R Keith Reeves Galit Alter Marcus Altfeld R Paul Johnson Mary Carrington David H O'Connor David T Evans |
| author_sort |
Arnaud D Colantonio |
| title |
KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif. |
| title_short |
KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif. |
| title_full |
KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif. |
| title_fullStr |
KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif. |
| title_full_unstemmed |
KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif. |
| title_sort |
kir polymorphisms modulate peptide-dependent binding to an mhc class i ligand with a bw6 motif. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/9c08f1e1496f4f9981d0ba1da7d7aa98 |
| work_keys_str_mv |
AT arnauddcolantonio kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT benjaminnbimber kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT williamjneidermyer kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT rkeithreeves kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT galitalter kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT marcusaltfeld kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT rpauljohnson kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT marycarrington kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT davidhoconnor kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif AT davidtevans kirpolymorphismsmodulatepeptidedependentbindingtoanmhcclassiligandwithabw6motif |
| _version_ |
1718424683523604480 |