Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci

Mary Carrington, Sophia Wang, Maureen P. Martin, Xiaojiang Gao, Mark Schiffman, Jie Cheng, Rolando Herrero, Ana Cecilia Rodriguez, Robert Kurman, Rodrigue Mortel, Peter Schwartz, Andrew Glass, Allan Hildesheim

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1069-1075
Number of pages7
JournalJournal of Experimental Medicine
Volume201
Issue number7
DOIs
StatePublished - Apr 4 2005

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Carrington, M., Wang, S., Martin, M. P., Gao, X., Schiffman, M., Cheng, J., Herrero, R., Rodriguez, A. C., Kurman, R., Mortel, R., Schwartz, P., Glass, A., & Hildesheim, A. (2005). Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. Journal of Experimental Medicine, 201(7), 1069-1075. https://doi.org/10.1084/jem.20042158