title: An NKG2D-mediated human lymphoid stress surveillance response with high interindividual variation.
abstract: DNA damage or other physicochemical stresses may increase the expression of major histocompatibility complex class I-related stress antigens, which then activate lymphocytes. This lymphoid stress surveillance (LSS) not only can limit tumor formation but may also promote immunopathology. MICA is a highly polymorphic human stress antigen implicated in tumor surveillance, inflammation, and transplant rejection. However, LSS has not been conclusively demonstrated in humans, and the functional role for MICA polymorphisms remains to be established. We show that MICA coding sequence polymorphisms substantially affected RNA and protein expression. All donors tested showed LSS responses of γδ T and natural killer cells, but unexpectedly, each was individually "tuned." Hence, some responded optimally to highly expressed alleles, whereas others responded better to lower MICA expression, challenging the orthodoxy that higher stress antigen levels promote greater responsiveness. These individual variations in LSS tuning may help explain patient-specific differences in tumor immune surveillance, transplant rejection, and inflammation, as well as provide insight into immune evasion and immunosuppression.
authors: Peter Gorer Department of Immunobiology, King's College London, UK.
authors: Seema
authors: S
authors: Shafi
authors: Peter Gorer Department of Immunobiology, King's College London, UK.|London Research Institute, Cancer Research UK, London, UK.
authors: Pierre
authors: P
authors: Vantourout
authors: School of Immunity and Infection, University of Birmingham, UK.
authors: Graham
authors: G
authors: Wallace
authors: School of Cancer Studies, University of Birmingham, UK.
authors: Ayman
authors: A
authors: Antoun
authors: Clinical Transplantation Department, Guy's Hospital, London, UK.|MRC Centre for Transplant Biology.
authors: Robert
authors: R
authors: Vaughan
authors: Clinical Transplantation Department, Guy's Hospital, London, UK.
authors: Miles
authors: M
authors: Stanford
authors: Peter Gorer Department of Immunobiology, King's College London, UK.|London Research Institute, Cancer Research UK, London, UK.|Comprehensive Biomedical Research Centre of Guy's and St Thomas' Hospitals and King's College London, London, UK.|MRC Centre for Transplant Biology.
authors: Adrian
authors: A
authors: Hayday
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D011110:Polymorphism, Genetic; D013312:Stress, Physiological / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K