High-throughput Characterization of HLA-E-presented CD94/NKG2x Ligands Reveals Peptides Which Modulate NK Cell Activation

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Aug 9

PMID 37558657

Authors

Brooke D Huisman

Ning Guan

Timo Ruckert

Lee Garner

Nishant K Singh

Andrew J McMichael

Geraldine M Gillespie

Chiara Romagnani

Michael E Birnbaum

Affiliations

Soon will be listed here.

Abstract

HLA-E is a non-classical class I MHC protein involved in innate and adaptive immune recognition. While recent studies have shown HLA-E can present diverse peptides to NK cells and T cells, the HLA-E repertoire recognized by CD94/NKG2x has remained poorly defined, with only a limited number of peptide ligands identified. Here we screen a yeast-displayed peptide library in the context of HLA-E to identify 500 high-confidence unique peptides that bind both HLA-E and CD94/NKG2A or CD94/NKG2C. Utilizing the sequences identified via yeast display selections, we train prediction algorithms and identify human and cytomegalovirus (CMV) proteome-derived, HLA-E-presented peptides capable of binding and signaling through both CD94/NKG2A and CD94/NKG2C. In addition, we identify peptides which selectively activate NKG2C NK cells. Taken together, characterization of the HLA-E-binding peptide repertoire and identification of NK activity-modulating peptides present opportunities for studies of NK cell regulation in health and disease, in addition to vaccine and therapeutic design.

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