HLA-E/peptide complexes differentially interact with NKG2A/CD94 and T cell receptors

The virtually monomorphic antigen presentation molecule HLA-E can present self- and non-self peptides to the NKG2A/CD94 co-receptor inhibitory complex expressed on natural killer (NK) cells and to T cell receptors (TCRs) expressed on T cells. HLA-E presents self-peptides to NKG2A/CD94 to regulate tissue homeostasis, whereas HLA-E restricted T cells mediate regulatory and cytotoxic responses toward pathogen-infected cells. In this study, we directly compared HLA-E/peptide recognition and signaling between NKG2A/CD94 and 2 HLA-E restricted TCRs that can recognize self-peptides or identical peptide mimics from the viral UL40 protein of cytomegalovirus using position substituted peptide variants. We show that position 7 is critical for interaction with NKG2A/CD94, whereas position 8 is important for interaction with the TCRs. The Arginine at position 5 of these peptides is an essential residue for recognition by both receptors. Thus, NKG2A/CD94 and TCRs have different requirements for recognition of peptides presented in HLA-E.

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Publication Details

Journal
The Journal of Immunology
Published
2025-03-14
DOI
https://doi.org/10.1093/jimmun/vkae068
Citations
6
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
4.78

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article

HLA-E/peptide complexes differentially interact with NKG2A/CD94 and T cell receptors

Tom H. M. Ottenhoff, Kees L. M. C. Franken, Marjolein van Wolfswinkel, Simone A. Joosten et al.
6 citations
The Journal of Immunology
Immune Cell Function and Interaction
4.78
article

HLA-E/peptide complexes differentially interact with NKG2A/CD94 and T cell receptors

Tom H. M. Ottenhoff, Kees L. M. C. Franken, Marjolein van Wolfswinkel, Simone A. Joosten, Peter Steinberger, Willem Jespers, Paula Ruibal, Linda Voogd, Gerard J. P. van Westen, Judith Leitner, Remco L. van den Broek
article en
6 citations

Abstract

The virtually monomorphic antigen presentation molecule HLA-E can present self- and non-self peptides to the NKG2A/CD94 co-receptor inhibitory complex expressed on natural killer (NK) cells and to T cell receptors (TCRs) expressed on T cells. HLA-E presents self-peptides to NKG2A/CD94 to regulate tissue homeostasis, whereas HLA-E restricted T cells mediate regulatory and cytotoxic responses toward pathogen-infected cells. In this study, we directly compared HLA-E/peptide recognition and signaling between NKG2A/CD94 and 2 HLA-E restricted TCRs that can recognize self-peptides or identical peptide mimics from the viral UL40 protein of cytomegalovirus using position substituted peptide variants. We show that position 7 is critical for interaction with NKG2A/CD94, whereas position 8 is important for interaction with the TCRs. The Arginine at position 5 of these peptides is an essential residue for recognition by both receptors. Thus, NKG2A/CD94 and TCRs have different requirements for recognition of peptides presented in HLA-E.

The Journal of ImmunologyVol. 214(4)
Leiden University (NL), Leiden University Medical Center (NL), Institute of Immunology (HR), Centre for Human Drug Research (NL), Medical University of Vienna (AT)
Leids Universitair Medisch Centrum, National Institutes of Health, National Institute of Allergy and Infectious Diseases
Openalex Percentile: Top 5%
Immune Cell Function and Interaction
4.78
DOIOpen Access PDFOpenAlex
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