title: Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in Hepatitis C virus infection outcome.
abstract: Natural killer cells are important in innate defense against viral infections. The interplay between stimulatory and inhibitory natural killer cell receptors and their corresponding human leukocyte antigen ligands are known to influence the outcome of acute Hepatitis C virus infection. Frequencies of NK receptor genes (8 inhibitory, 6 activating and 2 pseudogenes) and HLA class II alleles (DRB1, DQB1) were analyzed in 160 Puerto-Rican American drug users with Hepatitis C virus infection; 121 had chronic viremia (CV) and 39 were spontaneous clearance (SC). We further ruled out genetic stratification using short tandem repeats. Interaction between KIR gene receptor 2DL3/2DL3 and its ligand, C1/C1 of HLA-Cw alleles and spontaneous clearance was confirmed (p=0.03, OR=3.05). We also found a new interaction between the KIR receptor gene 2DL3 with HLA-DRB1*1201 (p=0.0001, OR=22) associated with SC, and an association of HLA DQB1*0501 (p=0.05, OR=0.30) with CV. Our findings suggested a role for MHC class II alleles in Hepatitis C virus peptide presentation to T cells together with NK ligand interaction involving pathways that will be useful for the development of immunotherapeutic interventions.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Viviana
authors.initials: V
authors.lastname: Romero
authors.forename: Jose
authors.initials: J
authors.lastname: Azocar
authors.forename: Joaquin
authors.initials: J
authors.lastname: Zúñiga
authors.forename: Olga P
authors.initials: OP
authors.lastname: Clavijo
authors.forename: Daniel
authors.initials: D
authors.lastname: Terreros
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Gu
authors.forename: Zaheed
authors.initials: Z
authors.lastname: Husain
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.forename: Christopher
authors.initials: C
authors.lastname: Amos
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: Yunis
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D015236:HLA-C Antigens / Q000235:genetics*; D016174:Hepacivirus / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D019966:Substance-Related Disorders / Q000150:complications / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014766:Viremia
chemical_list: D015236:HLA-C Antigens; D018936:Hepatitis C Antigens; D054340:Receptors, KIR