Specific Recognition of HLA-E, But Not Classical, HLA Class I Molecules by Soluble CD94/NKG2A and NK Cells

• Published in: The Journal of immunology (1950) Vol. 162; no. 1; pp. 305 - 313
• Main Authors: Brooks, Andrew G, Borrego, Francisco, Posch, Phillip E, Patamawenu, Apisit, Scorzelli, Christopher J, Ulbrecht, Matthias, Weiss, Elizabeth H, Coligan, John E
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.01.1999
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Antigens, CD - physiology; Base Sequence; Cell Line; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Dimerization; Histocompatibility Antigens Class I - metabolism; HLA Antigens - metabolism; HLA-E Antigens; Humans; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lectins, C-Type; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - physiology; Mice; Molecular Sequence Data; NK Cell Lectin-Like Receptor Subfamily D; Peptide Fragments - immunology; Peptide Fragments - metabolism; Protein Binding - immunology; Protein Sorting Signals - immunology; Protein Sorting Signals - metabolism; Solubility; Threonine - metabolism; Transfection - immunology; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.1.305

The CD94/NKG2 receptors expressed by subpopulations of NK cells and T cells have been implicated as receptors for a broad range of both classical and nonclassical HLA class I molecules. To examine the ligand specificity of CD94/NKG2 proteins, a soluble heterodimeric form of the receptor was produced and used in direct binding studies with cells expressing defined HLA class I/peptide complexes. We confirm that CD94/NKG2A specifically interacts with HLA-E and demonstrate that this interaction is dependent on the association of HLA-E with peptide. Moreover, no interaction between CD94/NKG2A and classical HLA class I molecules was observed, as assayed by direct binding of the soluble receptor or by functional assays using CD94/NKG2A+ NK cells. The role of the peptide associated with HLA-E in the interaction between HLA-E and CD94/NKG2A was also assessed. All class I leader sequence peptides tested bound to HLA-E and were recognized by CD94/NKG2A. However, amino acid variations in class I leader sequences affected the stability of HLA-E. Additionally, not all HLA-E/peptide complexes examined were recognized by CD94/NKG2A. Thus CD94/NKG2A recognition of HLA-E is controlled by peptide at two levels; first, peptide must stabilize HLA-E and promote cell surface expression, and second, the HLA-E/peptide complex must form the ligand for CD94/NKG2A.