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T‐cell stimulation and cytokine release induced by staphylococcal enterotoxin A (SEA) and the SEAD227A mutant
Author(s) -
HOLZER U.,
ORLIKOWSKY T.,
ZEHRER C.,
BETHGE W.,
DOHLSTEN M.,
KALLAND T.,
NIETHAMMER D.,
DANNECKER G. E.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00141.x
Subject(s) - enterotoxin , stimulation , mutant , microbiology and biotechnology , cytokine , staphylococcus aureus , biology , chemistry , immunology , bacteria , escherichia coli , biochemistry , endocrinology , genetics , gene
Previous work demonstrated that human cytotoxic T cells activated by superantigens can lyse major histocompatibility complex (MHC) class II‐positive target cells as well as MHC class II‐negative tumour cells coated with conjugates of monoclonal antibodies and superantigens. In order to decrease MHC class II affinity, and therefore unwanted binding of the superantigen staphylococcal enterotoxin A (SEA) to MHC class II molecules, a point mutation was introduced into the SEA gene. This mutation (SEAD227A) resulted in an approximately 3‐log reduction of affinity to human leucocyte antigen (HLA)‐DR, but cytotoxicity mediated by this mutant superantigen towards antibody‐labelled tumour cells is as efficient as cytotoxicity mediated by the native superantigen. We therefore compared the T‐cell activating potency of native and mutated SEA. Our data show that SEAD227A is 4‐ to 5‐log less effective than native SEA when activation of resting T cells is assayed in terms of blast formation, expression of cell surface activation markers and cytokine release. Furthermore, presenting either SEA or SEAD227A to MHC class II‐negative mononuclear cells by MHC class II‐negative tumour cells did not result in significant blast formation of T cells, up‐regulation of CD25 or cytokine release. This suggests that lysis of MHC class II‐negative tumour cells is efficiently induced by monoclonal antibody targeted superantigen, while activation of resting T cells requires additional co‐stimulatory signals.