Journal Article

Quantity of HLA-C surface expression and licensing of KIR2DL+ natural killer cells

Stern, Martin, Gonzalez, Asensio, Schmitter, Karin, Czaja, Karol, Infanti, Laura, Charoudeh, Hojjatollah Nozad, Schmied, Laurent, Terszowski, Grzegorz, Buser, Andreas

2012

Overview

Natural killer (NK) cells require interaction of inhibitory surface receptors with human leukocyte antigen (HLA) ligands during development to acquire functional competence in a process termed “licensing.” The quantity of HLA required for this process is unknown. Two polymorphisms affecting HLA-C surface expression (rs9264942 and rs67384697) have recently been identified, and shown to influence progression of HIV infection. We typed a cohort of healthy donors for the two HLA-C-related polymorphisms, KIR2DL1 and KIR2DL3 , and their respective HLA-C ligands and analyzed how HLA ligands influenced licensing status of killer cell immunoglobulin-like receptor (KIR)+ NK cells in terms of degranulation and cytokine production in response to HLA-deficient target cells. The presence of respective HLA class I ligands increased the function of KIR2DL1+ and KIR2DL3+ NK cells in a dose-dependent manner. In contrast, neither of the HLA-C-related polymorphisms nor the quantity of cell surface HLA-C had any significant effect on NK cell function. Interestingly, HLA-Cw7—an HLA-C allele with low surface expression—licensed KIR2DL3+ NK cells more strongly than any other KIR2DL3 ligand. The quantity of cell surface HLA-C does not appear to influence licensing of NK cells, and the HLA-C-related polymorphisms presumably influence HIV progression through factors unrelated to NK cell education.

• Publisher: Springer-Verlag,Springer Nature B.V
• Subject: Allergology / Antigens / Biomedical and Life Sciences / Biomedicine / Cell Biology / Cell surface / Cytokines / Degranulation / DNA - genetics / Gene Function / Gene polymorphism / Genotype / Histocompatibility antigen HLA / HIV / HIV Infections / HLA-C Antigens - genetics / HLA-C Antigens - metabolism / Human Genetics / Human immunodeficiency virus / Humans / Immunoglobulins / Immunology / Infection / Infections / Killer cell immunoglobulin-like receptors / Killer Cells, Natural - cytology / Killer Cells, Natural - metabolism / Leukocytes / Licenses / Licensing / Ligands / Lymphocytes / Natural killer cells / Original Paper / Polymerase Chain Reaction / Polymorphism / Polymorphism, Genetic - genetics / Potassium channels (inwardly-rectifying) / Receptors, KIR - genetics / Receptors, KIR - metabolism / Receptors, KIR2DL1 - genetics / Receptors, KIR2DL1 - metabolism / Receptors, KIR2DL2 - genetics / Receptors, KIR2DL2 - metabolism / Receptors, KIR2DL3 - genetics / Receptors, KIR2DL3 - metabolism / Viral infections