Saunders, Philippa M., MacLachlan, Bruce J., Pymm, Phillip, Illing, Patricia T., Deng, Yuanchen, Wong, Shu Cheng, Oates, Clare V. L., Purcell, Anthony W., Rossjohn, Jamie ![]() |
Abstract
Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*57:01, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*57:01, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*57:03, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.
Item Type: | Article |
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Date Type: | Published Online |
Status: | Published |
Schools: | Medicine |
Publisher: | National Academy of Sciences |
ISSN: | 0027-8424 |
Last Modified: | 07 Nov 2022 10:38 |
URI: | https://orca.cardiff.ac.uk/id/eprint/132923 |
Citation Data
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