The interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitope

Hdl Handle:
http://hdl.handle.net/10034/604551
Title:
The interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitope
Authors:
Saunders, Philippa M.; Vivian, Julian P.; Baschuk, Nikola; Beddoe, Travis; Widjaja, Jacqueline M.; O’Connor, Geraldine M.; Hitchen, Corinne; Pymm, Phillip; Andrews, Daniel M.; Gras, Stephanie; McVicar, Daniel W.; Rossjohn, Jamie; Brooks, Andrew G.
Abstract:
The killer cell Ig-like receptor 3DL1 (KIR3DL1) inhibits activation of NK cells upon interaction with HLA class I molecules such as HLA-B*57:01, which contains the Bw4 epitope spanning residues 77-83 (e.g., NLRIALR), and not with HLA allomorphs that possess the Bw6 motif (e.g., HLA-B*08:01), which differ at residues 77, 80, 81, 82, and 83. Although Bw4 residues Ile(80) and Arg(83) directly interact with KIR3DL1*001, their precise role in determining KIR3DL1-HLA-Bw4 specificity remains unclear. Recognition of HLA-B*57:01 by either KIR3DL1(+) NK cells or the NK cell line YTS transfected with KIR3DL1*001 was impaired by mutation of residues 80 and 83 of HLA-B*57:01 to the corresponding amino acids within the Bw6 motif. Conversely, the simultaneous introduction of three Bw4 residues at positions 80, 82, and 83 into HLA-B*08:01 conferred an interaction with KIR3DL1*001. Structural analysis of HLA-B*57:01, HLA-B*08:01, and mutants of each bearing substitutions at positions 80 and 83 revealed that Ile(80) and Arg(83) within the Bw4 motif constrain the conformation of Glu(76), primarily through a salt bridge between Arg(83) and Glu(76). This salt bridge was absent in HLA-Bw6 molecules as well as position 83 mutants of HLA-B*57:01. Mutation of the Bw4 residue Ile(80) also disrupted this salt bridge, providing further insight into the role that position 80 plays in mediating KIR3DL1 recognition. Thus, the strict conformation of HLA-Bw4 allotypes, held in place by the Glu(76)-Arg(83) interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the alpha1 helix that is less permissive for KIR3DL1 binding.
Affiliation:
Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; Cancer Immunology Program, Peter McCallum Cancer Institute, Melbourne, Victoria 3002, Australia; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Cancer and Inflammation Program, National Cancer Institute-Frederick, Frederick, MD 21702; and. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingom
Citation:
Saunders, P. M., Vivian, J. P., Baschuk, N., Beddoe, T., Widjaja, J., O’Connor, G. M., . . . Brooks, A. G. (2015). The Interaction of KIR3DL1*001 with HLA Class I Molecules Is Dependent upon Molecular Microarchitecture within the Bw4 Epitope. The Journal of Immunology, 194(2), 781-789. doi: 10.4049/jimmunol.1402542
Journal:
Journal of Immunology
Publication Date:
Jan-2015
URI:
http://hdl.handle.net/10034/604551
DOI:
10.4049/jimmunol.1402542
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282956/
Type:
Article
Language:
en_US
Description:
This article is not available through ChesterRep.
ISSN:
0022-1767
EISSN:
1550-6606
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorSaunders, Philippa M.en
dc.contributor.authorVivian, Julian P.en
dc.contributor.authorBaschuk, Nikolaen
dc.contributor.authorBeddoe, Travisen
dc.contributor.authorWidjaja, Jacqueline M.en
dc.contributor.authorO’Connor, Geraldine M.en
dc.contributor.authorHitchen, Corinneen
dc.contributor.authorPymm, Phillipen
dc.contributor.authorAndrews, Daniel M.en
dc.contributor.authorGras, Stephanieen
dc.contributor.authorMcVicar, Daniel W.en
dc.contributor.authorRossjohn, Jamieen
dc.contributor.authorBrooks, Andrew G.en
dc.date.accessioned2016-04-05T17:48:40Zen
dc.date.available2016-04-05T17:48:40Zen
dc.date.issued2015-01en
dc.identifier.citationSaunders, P. M., Vivian, J. P., Baschuk, N., Beddoe, T., Widjaja, J., O’Connor, G. M., . . . Brooks, A. G. (2015). The Interaction of KIR3DL1*001 with HLA Class I Molecules Is Dependent upon Molecular Microarchitecture within the Bw4 Epitope. The Journal of Immunology, 194(2), 781-789. doi: 10.4049/jimmunol.1402542en
dc.identifier.issn0022-1767en
dc.identifier.doi10.4049/jimmunol.1402542en
dc.identifier.urihttp://hdl.handle.net/10034/604551en
dc.descriptionThis article is not available through ChesterRep.en
dc.description.abstractThe killer cell Ig-like receptor 3DL1 (KIR3DL1) inhibits activation of NK cells upon interaction with HLA class I molecules such as HLA-B*57:01, which contains the Bw4 epitope spanning residues 77-83 (e.g., NLRIALR), and not with HLA allomorphs that possess the Bw6 motif (e.g., HLA-B*08:01), which differ at residues 77, 80, 81, 82, and 83. Although Bw4 residues Ile(80) and Arg(83) directly interact with KIR3DL1*001, their precise role in determining KIR3DL1-HLA-Bw4 specificity remains unclear. Recognition of HLA-B*57:01 by either KIR3DL1(+) NK cells or the NK cell line YTS transfected with KIR3DL1*001 was impaired by mutation of residues 80 and 83 of HLA-B*57:01 to the corresponding amino acids within the Bw6 motif. Conversely, the simultaneous introduction of three Bw4 residues at positions 80, 82, and 83 into HLA-B*08:01 conferred an interaction with KIR3DL1*001. Structural analysis of HLA-B*57:01, HLA-B*08:01, and mutants of each bearing substitutions at positions 80 and 83 revealed that Ile(80) and Arg(83) within the Bw4 motif constrain the conformation of Glu(76), primarily through a salt bridge between Arg(83) and Glu(76). This salt bridge was absent in HLA-Bw6 molecules as well as position 83 mutants of HLA-B*57:01. Mutation of the Bw4 residue Ile(80) also disrupted this salt bridge, providing further insight into the role that position 80 plays in mediating KIR3DL1 recognition. Thus, the strict conformation of HLA-Bw4 allotypes, held in place by the Glu(76)-Arg(83) interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the alpha1 helix that is less permissive for KIR3DL1 binding.en
dc.language.isoen_USen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282956/en
dc.subjectNatural Killer Cellsen
dc.subjectKIRen
dc.titleThe interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitopeen_US
dc.typeArticleen
dc.identifier.eissn1550-6606en
dc.contributor.departmentDepartment of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; Cancer Immunology Program, Peter McCallum Cancer Institute, Melbourne, Victoria 3002, Australia; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Cancer and Inflammation Program, National Cancer Institute-Frederick, Frederick, MD 21702; and. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingomen
dc.identifier.journalJournal of Immunologyen
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