Selective modulation of superantigen-induced responses by streptococcal cysteine protease.
Streptococcal pyrogenic exotoxin (Spe) B, a streptococcal cysteine protease, is believed to be important in group A streptococcal (GAS) pathogenesis. The present study examined the effect of SpeB on the activity of superantigenic exotoxins secreted by M1T1 GAS isolates. The proliferative response of human lymphocytes to culture supernatant (SUP) from an SpeB(+) isolate increased significantly (P<.05) when the isolate was grown with N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]-agmatine, a cysteine protease inhibitor. The lymphocyte-stimulating activity of SUP from a spontaneous SpeB(-) variant or SpeB(-) knockout (DeltaSpeB) mutant was also significantly higher than that of SUP from the SpeB(+) parent isolate (P<.001). The addition of recombinant SpeB to the DeltaSpeB mutant reduced the lymphocyte response to a level comparable to that with the SpeB(+) isolate. SpeB affected superantigens that stimulate cells expressing T cell receptor Vbeta (TCRBV)-4, TCRBV7, and TCRBV8 but not those that stimulate TCRBV2. SpeB has a selective proteolytic effect on GAS superantigens.
Kansal
Rita G
RG
Veterans Affairs Medical Center, Research Service, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Nizet
Victor
V
Jeng
Arthur
A
Chuang
Woei-Jer
WJ
Kotb
Malak
M
D001426:Bacterial Proteins; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013291:Streptococcus / Q000201:enzymology* / Q000276:immunology*; D018089:Superantigens / Q000276:immunology* / Q000378:metabolism*
D001426:Bacterial Proteins; D017077:Culture Media, Conditioned; D015853:Cysteine Proteinase Inhibitors; D018089:Superantigens; D003546:Cysteine Endopeptidases; C042477:streptopain; D007930:Leucine; C024974:E 64