title: Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci.
abstract: Killer immunoglobulin-like receptor (KIR) recognition of specific human histocompatibility leukocyte antigen (HLA) class I allotypes contributes to the array of receptor-ligand interactions that determine natural killer (NK) cell response to its target. Contrasting genetic effects of KIR/HLA combinations have been observed in infectious and autoimmune diseases, where genotypes associated with NK cell activation seem to be protective or to confer susceptibility, respectively. We show here that combinations of KIR and HLA loci also affect the risk of developing cervical neoplasia. Specific inhibitory KIR/HLA ligand pairs decrease the risk of developing neoplasia, whereas the presence of the activating receptor KIR3DS1 results in increased risk of disease, particularly when the protective inhibitory combinations are missing. These data suggest a continuum of resistance conferred by NK cell inhibition to susceptibility involving NK cell activation in the development of cervical neoplasia and underscore the pervasive influence of KIR/HLA genetic variation in human disease pathogenesis.
authors.affiliation: Basic Research Program, Laboratory of Genomic Diversity, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21702, USA. carringt@ncifcrf.gov
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Sophia
authors.initials: S
authors.lastname: Wang
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Martin
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Robert
authors.initials: R
authors.lastname: Kurman
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Mortel
authors.forename: Peter
authors.initials: P
authors.lastname: Schwartz
authors.forename: Andrew
authors.initials: A
authors.lastname: Glass
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
mesh_terms: D016022:Case-Control Studies; D003364:Costa Rica; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000276:immunology*; D005838:Genotype; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology*
chemical_list: D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1