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PMID: 8335347 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Lack of complete correlation between emetic and T-cell-stimulatory activities of staphylococcal enterotoxins.

Infection and immunity ·Vol. 61 ·No. 8 ·1993-08-00 ·Pages 3175-83

Harris TO, Grossman D, Kappler JW, Marrack P, Rich RR, Betley MJ

Abstract

This study examined the emetic activity of several staphylococcal enterotoxin type A and B (SEA and SEB, respectively) mutants that had either one or two amino acid residue substitutions. New sea gene mutations were constructed by site-directed mutagenesis; gene products were obtained with glycine residues at position 25, 47, 48, 81, 85, or 86 of mature SEA. Culture supernatants from Staphylococcus aureus RN4220, or derivatives containing either sea or a sea mutation, were analyzed for the ability to stimulate proliferation of murine splenocytes, as determined by incorporation of [3H]thymidine. Culture supernatants containing SEA-N25G (a SEA mutant with a substitution of glycine for the asparagine residue at position 25), SEA-F47G, or SEA-L48G did not stimulate T-cell proliferation, unlike supernatants containing the other substitution mutants. Purified preparations of SEA-N25G had weak activity and those of SEA-F47G and SEA-L48G had essentially no activity in the T-cell proliferation assay. All mutants except SEA-V85G, which was degraded by monkey stomach lavage fluid in vitro, were tested for emetic activity. SEA-C106A and two SEB mutants, SEB-D9N/N23D and SEB-F44S (previously referred to as BR-257 and BR-358, respectively), whose construction and altered immunological properties have been reported previously, were also tested in the emetic assay. Each mutant was initially administered intragastrically at doses of 75 to 100 micrograms per animal; if none of the animals responded, the dose was increased four-to fivefold. SEA-F47G, SEA-C106A, and SEB-D9N/N23D were the only mutants that did not induce vomiting at either dose tested; these three mutants had reduced immunological activity. However, there was not a perfect correlation between immunological and emetic activities; SEA-L48G and SEB-F44S retained emetic activity, although they had essentially no T-cell-stimulatory activity. These studies suggest that these two activities can be dissociated.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Enterotoxins/chemistry,immunology,toxicity Female Lymphocyte Activation Macaca mulatta Mice Mice, Inbred BALB C Molecular Sequence Data Mutation Staphylococcus aureus/pathogenicity Structure-Activity Relationship T-Lymphocytes/immunology Vomiting/chemically induced
Chemicals
Enterotoxins enterotoxin A, Staphylococcal enterotoxin B, staphylococcal
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Harris T O
Department of Bacteriology, University of Wisconsin-Madison 53706.
Grossman D
Kappler J W
Marrack P
Rich R R
Betley M J
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.61.8.3175-3183.1993
Published
1993-08-00
Pages
3175-83
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC280985
Subset
IM
Grants
NIAID NIH HHS · AI-15394 · United States
NIAID NIH HHS · AI-30036 · United States
NIAID NIH HHS · AI25574 · United States
External Links
PubMed source DOI: 10.1128/iai.61.8.3175-3183.1993 PMC Full Text View journal details
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