TY - JOUR
T1 - Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci
AU - Carrington, Mary
AU - Wang, Sophia
AU - Martin, Maureen P.
AU - Gao, Xiaojiang
AU - Schiffman, Mark
AU - Cheng, Jie
AU - Herrero, Rolando
AU - Rodriguez, Ana Cecilia
AU - Kurman, Robert
AU - Mortel, Rodrigue
AU - Schwartz, Peter
AU - Glass, Andrew
AU - Hildesheim, Allan
PY - 2005/4/4
Y1 - 2005/4/4
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20042158
DO - 10.1084/jem.20042158
M3 - Article
C2 - 15809352
AN - SCOPUS:20244374101
SN - 0022-1007
VL - 201
SP - 1069
EP - 1075
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -