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

Abstract

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.

• Authors: Hojjatollah Nozad Charoudeh, Laurent Schmied, Asensio Gonzalez, Grzegorz Terszowski, Karol Czaja, Karin Schmitter, Laura Infanti, Andreas Buser, Martin Stern
• Journal: Immunogenetics (Immunogenetics) Vol. 64 Issue 10 Pg. 739-45 (Oct 2012) ISSN: 1432-1211 [Electronic] United States
• PMID: 22772778 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-C Antigens
• Ligands
• Receptors, KIR
• Receptors, KIR2DL1
• Receptors, KIR2DL2
• Receptors, KIR2DL3
• DNA

Topics

• DNA (genetics)
• Genotype
• HIV Infections
• HLA-C Antigens (genetics, metabolism)
• Humans
• Killer Cells, Natural (cytology, metabolism)
• Leukocytes
• Ligands
• Polymerase Chain Reaction
• Polymorphism, Genetic (genetics)
• Receptors, KIR (genetics, metabolism)
• Receptors, KIR2DL1 (genetics, metabolism)
• Receptors, KIR2DL2 (genetics, metabolism)
• Receptors, KIR2DL3 (genetics, metabolism)