An NKG2D-Mediated Human Lymphoid Stress Surveillance Response with High Interindividual Variation

S Shafi, P Vantourout, Graham Wallace, Ayman Antoun, R Vaughan, M Stanford, A Hayday

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 gamma delta 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.
Original languageEnglish
Pages (from-to)113ra124
JournalScience Translational Medicine
Volume3
Issue number113
DOIs
Publication statusPublished - 1 Dec 2011

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