Analysis of mechanisms by which NK cells acquire increased cytotoxicity against class I MHC-eliminated targets.
Acid treatment, where cells are exposed to 0.2 M citric acid buffer at pH 3 for 2 min, was described in a previous paper to be a method which specifically eliminates class I MHC antigens from the membrane of viable cells. We applied this method to characterize functional roles of class I MHC antigens on the target cells in NK cell cytotoxicity. When NK target cells, U937, Molt-4, and Raji, were subjected to acid treatment, the treated cells lost their surface class I MHC antigens and became more sensitive to NK cell killing. On the other hand, the susceptibility of K562 cells which initially lacked class I MHC antigens did not significantly change after such treatment. We then examined the mechanism which enables NK cells to become more cytotoxic against class I MHC antigen-eliminated target cells. Single cell binding assay and cold target inhibition assay demonstrated that class I MHC antigen-eliminated target cells did not acquire high binding affinity to NK cells. However, the interaction between NK cells and class I MHC antigen-eliminated targets resulted in a greater increase in production of NKCF-like factor than did the interaction between NK cells and untreated targets. Class I MHC antigen-eliminated targets did not acquire high killer susceptibility to NKCF-like factor. The present study utilizing the acid treatment method confirmed that surface class I MHC antigens on the targets are important immunoregulatory molecules not only for cytotoxic T lymphocytes but also for NK cells and elucidated some of the underlying mechanisms.
Sugawara
S
S
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.
Abo
T
T
Itoh
H
H
Kumagai
K
K
D000143:Acids / Q000494:pharmacology; D000954:Antigens, Surface / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010641:Phenotype; D014407:Tumor Cells, Cultured
D000143:Acids; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I