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

The Journal of Immunology, vol. 214, pp. 595–605

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.

Authors 11

1. Linda Voogd Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center for Infectious Diseases, Leiden University Medical Center , Leiden,

   Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

2. Remco L. van den Broek Aachen Division of Medicinal Chemistry Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University , Leiden,

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

3. Marjolein van Wolfswinkel Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center for Infectious Diseases, Leiden University Medical Center , Leiden,

   Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

4. Kees L. M. C. Franken Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center for Infectious Diseases, Leiden University Medical Center , Leiden,

   Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

5. Paula Ruibal Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center for Infectious Diseases, Leiden University Medical Center , Leiden,

   Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

6. Willem Jespers Aachen Division of Medicinal Chemistry Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University , Leiden,

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

7. Judith Maria Leitner

   Medical University of Vienna

   Affiliation as printed

   Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna , Vienna,

   Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria

8. Peter Steinberger

   Medical University of Vienna

   Affiliation as printed

   Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna , Vienna,

   Centre for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria

9. Gerard J. P. van Westen Aachen Division of Medicinal Chemistry Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University , Leiden,

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands

10. Tom H. M. Ottenhoff Aachen

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Leiden University Center for Infectious Diseases, Leiden University Medical Center , Leiden,

    Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

11. Simone A. Joosten corresponding Aachen

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Leiden University Center for Infectious Diseases, Leiden University Medical Center , Leiden,

    Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands