Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected slow progressors

• Published in: Clinical immunology (Orlando, Fla.) Vol. 143; no. 3; pp. 246 - 255
• Main Authors: Kamya, Philomena, Tallon, Benjamin, Melendez-Pena, Carlos, Parsons, Matthew S., Migueles, Stephen A., Connors, Mark, Miconiatis, Sofia, Song, Rujun, Boulet, Salix, Bruneau, Julie, Tremblay, Cecile L., Bernard, Nicole F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.06.2012; Elsevier
• Subjects: Adult; Aged; Allergy and Immunology; Biological and medical sciences; CD4 Lymphocyte Count; Degranulation; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gamma -Interferon; Histocompatibility antigen HLA; HIV Infections - immunology; HLA-B Antigens - immunology; HLA-C Antigens - immunology; HLA-ligands; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin-like receptors; Immunopathology; Infectious diseases; K562 Cells; Killer Cells, Natural - immunology; Killer-Immunoglobulin-like Receptors; Medical sciences; Middle Aged; Natural Killer (NK) cells; Natural killer cells; NK function; Peripheral blood mononuclear cells; Potassium channels (inwardly-rectifying); Receptors, KIR - immunology; Self; Substance P; Tumor necrosis factor- alpha; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Young Adult; Killer-Immunoglobulin-like Receptors; Natural Killer (NK) cells; NK function; HLA-ligands; Immunopathology; HLA-System; Immunoglobulins; Ligand; Major histocompatibility system; Killer immunoglobulin like receptor; HLA-C-Locus; AIDS; Killer-Immunoglobulin-like; Immune deficiency; Infection; Natural killer cell; Receptors; Immunology; Viral disease; T-Lymphocyte; Class I histocompatibility antigen; HLA-B-Locus; Biological receptor
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2012.01.001

Inhibitory Killer Immunoglobulin-like Receptors (iKIR) interact with their ligands, HLA molecules, to license Natural Killer (NK) cells for functional competence. Previous studies stimulating peripheral blood mononuclear cells (PBMCs) with the HLA-devoid K562 cell line revealed that NK cells from individuals with an iKIR encoded by the KIR3DL1 locus with self HLA-Bw4 as their ligands, had higher frequencies of tri-functional NK cells that expressed the degranulation marker CD107a and secreted Interferon-γ and Tumor Necrosis Factor-α than those from individuals who were homozygous for HLA-Bw6 alleles, which are not ligands for these iKIR. To assess the effect of other iKIR to self-HLA (S-iKIR) on the NK cell response, we compared HIV-infected slow progressors (SP) carrying S-iKIR to HLA-C alleles with or without S-iKIR to HLA-Bw4. We show that S-iKIR to HLA-B and C alleles differ in their contribution to NK cell functional potential in HIV-infected SP upon stimulation with K562 targets. ► HLA antigens bind inhibitory Killer immunoglobulin-like receptors (iKIR). ► HLA and iKIR interact to license NK cells for functional competence. ► The impact of iKIR to self HLA-B and C was compared in HIV+ and HIV- subjects. ► S-iKIR to HLA-C contribute little to NK function in HIV infected slow progressors. ► S-iKIR to both HLA-B and HLA-C contribute to NK function in uninfected subjects.