Research ArticleHuman Immunology

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

Science Translational Medicine  14 Dec 2011:
Vol. 3, Issue 113, pp. 113ra124
DOI: 10.1126/scitranslmed.3002922

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


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.

Footnotes

  • * These authors contributed equally to this work.

View Full Text