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

Philippa M Saunders, Julian P Vivian, Nikola Baschuk, Travis C Beddoe, Jacqueline M L Widjaja, Geraldine M O'Connor, Corinne R Hitchen, Phillip Gordon Pymm, Daniel M K Andrews, Stephanie Gras, Daniel W McVicar, Jamie Rossjohn, Andrew G Brooks

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

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 Ile80 and Arg83 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 Ile80 and Arg83 within the Bw4 motif constrain the conformation of Glu76, primarily through a salt bridge between Arg83 and Glu76. 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 Ile80 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 Glu76-Arg83 interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the alpha1 helix that is less permissive for KIR3DL1 binding.
Original languageEnglish
Pages (from-to)781 - 789
Number of pages9
JournalJournal of Immunology
Volume194
Issue number2
DOIs
Publication statusPublished - 2015

Cite this

Saunders, Philippa M ; Vivian, Julian P ; Baschuk, Nikola ; Beddoe, Travis C ; Widjaja, Jacqueline M L ; O'Connor, Geraldine M ; Hitchen, Corinne R ; Pymm, Phillip Gordon ; Andrews, Daniel M K ; Gras, Stephanie ; McVicar, Daniel W ; Rossjohn, Jamie ; Brooks, Andrew G. / The interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitope. In: Journal of Immunology. 2015 ; Vol. 194, No. 2. pp. 781 - 789.
@article{d9b7b9eae1274a47b07b7f8aa3d1c69f,
title = "The interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitope",
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 Ile80 and Arg83 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 Ile80 and Arg83 within the Bw4 motif constrain the conformation of Glu76, primarily through a salt bridge between Arg83 and Glu76. 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 Ile80 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 Glu76-Arg83 interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the alpha1 helix that is less permissive for KIR3DL1 binding.",
author = "Saunders, {Philippa M} and Vivian, {Julian P} and Nikola Baschuk and Beddoe, {Travis C} and Widjaja, {Jacqueline M L} and O'Connor, {Geraldine M} and Hitchen, {Corinne R} and Pymm, {Phillip Gordon} and Andrews, {Daniel M K} and Stephanie Gras and McVicar, {Daniel W} and Jamie Rossjohn and Brooks, {Andrew G}",
year = "2015",
doi = "10.4049/jimmunol.1402542",
language = "English",
volume = "194",
pages = "781 -- 789",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

The interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitope. / Saunders, Philippa M; Vivian, Julian P; Baschuk, Nikola; Beddoe, Travis C; Widjaja, Jacqueline M L; O'Connor, Geraldine M; Hitchen, Corinne R; Pymm, Phillip Gordon; Andrews, Daniel M K; Gras, Stephanie; McVicar, Daniel W; Rossjohn, Jamie; Brooks, Andrew G.

In: Journal of Immunology, Vol. 194, No. 2, 2015, p. 781 - 789.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitope

AU - Saunders, Philippa M

AU - Vivian, Julian P

AU - Baschuk, Nikola

AU - Beddoe, Travis C

AU - Widjaja, Jacqueline M L

AU - O'Connor, Geraldine M

AU - Hitchen, Corinne R

AU - Pymm, Phillip Gordon

AU - Andrews, Daniel M K

AU - Gras, Stephanie

AU - McVicar, Daniel W

AU - Rossjohn, Jamie

AU - Brooks, Andrew G

PY - 2015

Y1 - 2015

N2 - 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 Ile80 and Arg83 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 Ile80 and Arg83 within the Bw4 motif constrain the conformation of Glu76, primarily through a salt bridge between Arg83 and Glu76. 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 Ile80 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 Glu76-Arg83 interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the alpha1 helix that is less permissive for KIR3DL1 binding.

AB - 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 Ile80 and Arg83 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 Ile80 and Arg83 within the Bw4 motif constrain the conformation of Glu76, primarily through a salt bridge between Arg83 and Glu76. 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 Ile80 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 Glu76-Arg83 interaction, facilitates KIR3DL1 binding, whereas Bw6 allotypes present a platform on the alpha1 helix that is less permissive for KIR3DL1 binding.

UR - http://www.jimmunol.org/content/194/2/781.full.pdf+html

U2 - 10.4049/jimmunol.1402542

DO - 10.4049/jimmunol.1402542

M3 - Article

VL - 194

SP - 781

EP - 789

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -