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. 1997 Jan;90(1):74–80. doi: 10.1046/j.1365-2567.1997.00141.x

T-cell stimulation and cytokine release induced by staphylococcal enterotoxin A (SEA) and the SEAD227A mutant.

U Holzer 1, T Orlikowsky 1, C Zehrer 1, W Bethge 1, M Dohlsten 1, T Kalland 1, D Niethammer 1, G E Dannecker 1
PMCID: PMC1456718  PMID: 9038715

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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