학술논문
HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses
Document Type
Original Paper
Author
Lin, Zhansong; Bashirova, Arman A.; Viard, Mathias; Garner, Lee; Quastel, Max; Beiersdorfer, Maya; Kasprzak, Wojciech K.; Akdag, Marjan; Yuki, Yuko; Ojeda, Pedro; Das, Sudipto; Andresson, Thorkell; Naranbhai, Vivek; Horowitz, Amir; McMichael, Andrew J.; Hoelzemer, Angelique; Gillespie, Geraldine M.; Garcia-Beltran, Wilfredo F.; Carrington, Mary
Source
Nature Immunology. 24(7):1087-1097
Subject
Language
English
ISSN
1529-2908
1529-2916
1529-2916
Abstract
Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that among 16 common classical HLA class I SP variants, only 6 can be efficiently processed to generate epitopes that enable CD94/NKG2 engagement, which we term ‘functional SPs’. The single functional HLA-B SP, known as HLA-B/−21M, induced high HLA-E expression, but conferred the lowest receptor recognition. Consequently, HLA-B/−21M SP competes with other SPs for providing epitope to HLA-E and reduces overall recognition of target cells by CD94/NKG2A, calling for reassessment of previous disease models involving HLA-B/−21M. Genetic population data indicate a positive correlation between frequencies of functional SPs in humans and corresponding cytomegalovirus mimics, suggesting a means for viral escape from host responses. The systematic, quantitative approach described herein will facilitate development of prediction algorithms for accurately measuring the impact of CD94/NKG2–HLA-E interactions in disease resistance/susceptibility.
Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors. Carrington and colleagues provide comprehensive analysis of classical HLA class I SP variants and show that these can determine CD94/NKG2–HLA-E engagement.
Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors. Carrington and colleagues provide comprehensive analysis of classical HLA class I SP variants and show that these can determine CD94/NKG2–HLA-E engagement.