T cell receptor V gene usage by human T cells stimulated with the superantigen streptococcal M protein.

Tomai, Mark A.; Aelion, Jacob; Dockter, Michael E.; Majumdar, Gipsy; Spinella, Dominic G.; Kotb, Malak

doi:10.1084/jem.174.1.285

Cited by 102 publications

(75 citation statements)

References 12 publications

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“…cDNA (5 l) was aliquoted and amplified in the presence of 1 l of each primers (10 M) either with V␣ family-specific 5Ј primers and 3Ј C␣ primers to generate a 320-to 410-bp product or V␤ family-specific 5Ј primers and 3Ј C␤ primers to generate a 170-to 220-bp product (41,42). As an internal control, two additional reactions were run, one containing 5Ј forward and 3Ј reverse C␤ primers to generate a 200-bp product (43) and the other containing 5Ј forward and 3Ј reverse C␣ primer to generate a 600-bp product (41). All of the primers were produced by MWG Biotec (Ebersberg, Germany).…”

Section: Analysis Of Tcr V␣ and V␤ Repertoire Using Rt-pcrmentioning

confidence: 99%

Staphylococcal Enterotoxin H Induces Vα-Specific Expansion of T Cells

Petersson

Pettersson

Skartved

et al. 2003

The Journal of Immunology

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Staphylococcal enterotoxin H (SEH) is a bacterial superantigen secreted by Staphylococcus aureus. Superantigens are presented on the MHC class II and activate large amounts of T cells by cross-linking APC and T cells. In this study, RT-PCR was used to show that SEH stimulates human T cells via the Vα domain of TCR, in particular Vα10 (TRAV27), while no TCR Vβ-specific expansion was seen. This is in sharp contrast to all other studied bacterial superantigens, which are highly specific for TCR Vβ. It was further confirmed by flow cytometry that SEH stimulation does not alter the levels of certain TCR Vβ. In a functional assay addressing cross-reactivity, Vβ binding superantigens were found to form one group, whereas SEH has different properties that fit well with Vα reactivity. As SEH binds on top of MHC class II, an interaction between MHC and TCR upon SEH binding is not likely. This concludes that the specific expansion of TCR Vα is not due to contacts between MHC and TCR, instead we suggest that SEH directly interacts with the TCR Vα domain.

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Section: Analysis Of Tcr V␣ and V␤ Repertoire Using Rt-pcrmentioning

confidence: 99%

Staphylococcal Enterotoxin H Induces Vα-Specific Expansion of T Cells

Petersson

Pettersson

Skartved

et al. 2003

The Journal of Immunology

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“…Mutant toxins were generated as previously described (Kline andCollins, 1996). et al, 1991;Braun et al, 1993;Leonard et al, 1991;Tomai et al, 1992). By using a commercially available Ab that recognizes CD3-positive cells (mAb UCHT-1) in conjunction with anti-V␤ mAbs, we examined the levels of V␤2-, 12-, and 14-positive T-cell blasts resulting from stimulation with the mutant and allelic toxin forms.…”

Section: Resultsmentioning

confidence: 99%

“…The superantigenic activity of SpeA is believed to be responsible for symptoms associated with STSS. SpeA stimulates T cells bearing V␤ chains 2, 12, 14, and 15 (Abe et al, 1991;Braun et al, 1993;Leonard et al, 1991;Tomai et al, 1992), and the activated T cells release the bioactive cytokines IL-2, TNF-␣, and IFN-␥. The symptoms of STSS are attributed to this considerable cytokine production (Alouf et al, 1991;Bohach et al, 1990;Marrack and Kappler, 1990).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the interaction between the bacterial superantigen streptococcal pyrogenic exotoxin A (SpeA) and the human T‐cell receptor

1997

Molecular Microbiology

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SummaryStreptococcus pyogenes that produces the bacterial superantigen streptococcal pyrogenic exotoxin A (SpeA) is associated with outbreaks of streptococcal toxic shock syndrome (STSS) in the United States and Europe. SpeA stimulates V␤2.1, 12.2, 14.1, and 15.1-positive T cells, and the lymphokine production from the activated T cells is believed to result in the symptoms associated with STSS. The T-cell receptor (TCR)-SpeA interaction is crucial for superantigenic activity, and studies were undertaken to determine regions of both SpeA and the TCR involved in the formation of MHC/SpeA/TCR complexes. Previously, recombinant toxins encoded by speA alleles 1, 2, and 3 as well as toxins resulting from 19 distinct point mutations in speA1 were generated. Here, these 22 toxin forms were incubated with human peripheral blood mononuclear cells (PBMCs), and the percentages of T-cell blasts bearing V␤ chains 2.1, 12.2, and 14.1 were quantified by flow cytometry. The analysis indicates that the residues of SpeA needed for a productive TCR interaction differ for each V␤ chain examined. An amino acid substitution at only one site significantly affected the toxin's ability to stimulate V␤2.1-expressing T cells, three individual amino acid substitutions resulted in significant loss of ability to stimulate V␤12.2-expressing T cells, and substitution at 13 individual sites significantly affected the ability to stimulate V␤14.1-expressing T cells. To elucidate the regions of the V␤ chains that interacted with SpeA, synthetic peptides representative of the human V␤12.2 complementary-determining regions (CDRs) 1, 2, and 4 were used to block the SpeA-mediated proliferation of human PBMCs. The CDR1, CDR2 and CDR4 peptides were each able to block proliferation, with the activity of CDR1 > CDR2 > CDR4. Combinations of CDR1 peptide with CDR2 or CDR4 peptides allosterically enhanced the ability of each to block proliferation, suggesting SpeA has distinct binding sites for the CDR loops.

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“…These aspects are currently under investigation. However, the streptococcal erythrogenic toxins A and C have been reported to have superantigen-like activity [25], and erythrogenic toxin C has been described as activating the YjH^ subset in vitro [26]. The similarities between the streptococcal-induced disorder and staphylococcal toxic shock syndrome may relate to the considerable molecular homology between streptococcal toxins A and C, and staphylococcal enterotoxins, including TSST-1 [27].…”

Section: Discussionmentioning

confidence: 99%

Streptococcal toxic shock-like syndrome: evidence of superantigen activity and its effects on T lymphocyte subsetsin vivo

Michie

Scott

Cheesbrough

et al. 1994

Clinical and Experimental Immunology

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SUMMARYToxic shock-like syndrome is a serious complication of invasive streptococcal disease. The syndrome is believed to be the consequence of exposure to exotoxins produced by the infecting organisms which behave as superantigens. We describe two patients who fulfilled clinical criteria for this syndrome, one of whom died. Streptococci isolated from both patients were found to produce a mitogen specific for the V/32''" T lymphocyte subset in vitro, which had the characteristics of a superantigen. The phenotype and function of lymphocytes collected from both patients during the acute phase of their illness demonstrated a marked reduction in circulating CD4''" ('helper') and CD45RA''' ('naive') T lymphocytes expressing the V/32 chain, and an increase of those expressing CD8, CD45RO and the V/32 chain. This effect resolved within 4 weeks in the patient who survived. Proliferation assays demonstrated no T cell anergy in either patient. Stimulation of lymphocytes by superantigen in these clinical situations does not appear to cause permanent deletion of T cell subsets, as has been observed in animal models.

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T cell receptor V gene usage by human T cells stimulated with the superantigen streptococcal M protein.

Cited by 102 publications

References 12 publications

Staphylococcal Enterotoxin H Induces Vα-Specific Expansion of T Cells

Staphylococcal Enterotoxin H Induces Vα-Specific Expansion of T Cells

Analysis of the interaction between the bacterial superantigen streptococcal pyrogenic exotoxin A (SpeA) and the human T‐cell receptor

Streptococcal toxic shock-like syndrome: evidence of superantigen activity and its effects on T lymphocyte subsetsin vivo

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