Functional analysis of the TCR binding domain of toxic shock syndrome toxin-1 predicts further diversity in MHC class II/superantigen/TCR ternary complexes

John K McCormick; Timothy J Tripp; Andrea S Llera; Eric J Sundberg; Martin M Dinges; Roy A Mariuzza; Patrick M Schlievert

doi:10.4049/jimmunol.171.3.1385

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Functional analysis of the TCR binding domain of toxic shock syndrome toxin-1 predicts further diversity in MHC class II/superantigen/TCR ternary complexes

Journal article

Peer reviewed

Functional analysis of the TCR binding domain of toxic shock syndrome toxin-1 predicts further diversity in MHC class II/superantigen/TCR ternary complexes

John K McCormick, Timothy J Tripp, Andrea S Llera, Eric J Sundberg, Martin M Dinges, Roy A Mariuzza and Patrick M Schlievert

The Journal of immunology (1950), Vol.171(3), pp.1385-1392

08/01/2003

DOI: 10.4049/jimmunol.171.3.1385

PMID: 12874229

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Abstract

Superantigens (SAGs) aberrantly alter immune system function through simultaneous interaction with lateral surfaces of MHC class II molecules on APCs and with particular variable regions of the TCR beta-chain (Vbeta). To further define the interface between the bacterial SAG toxic shock syndrome toxin-1 (TSST-1) and the TCR, we performed alanine scanning mutagenesis within the putative TCR binding region of TSST-1 along the central alpha helix adjacent to the N-terminal alpha helix and the beta7-beta9 loop as well as with two universally conserved SAG residues (Leu(137) and Tyr(144) in TSST-1). Mutants were analyzed for multiple functional activities, and various residues appeared to play minor or insignificant roles in the TCR interaction. The locations of six residues (Gly(16), Trp(116), Glu(132), His(135), Gln(136), and Gln(139)), each individually critical for functional activity as well as direct interaction with the human TCR Vbeta2.1-chain, indicate that the interface occurs in a novel region of the SAG molecule. Based on these data, a model of the MHC/TSST-1/TCR ternary complex predicts similarities seen with other characterized SAGs, although the CDR3 loop of Vbeta2.1 is probably involved in direct SAG-TCR molecular interactions, possibly contributing to the TCR Vbeta specificity of TSST-1.

Protein Binding - genetics

Spleen - immunology

Mitogens - pharmacology

Fever - microbiology

Humans

Receptors, Antigen, T-Cell, alpha-beta - chemistry

Amino Acid Substitution - immunology

Shock, Septic - immunology

Superantigens - metabolism

Bacterial Toxins

Histocompatibility Antigens Class II - metabolism

Fever - immunology

Disease Models, Animal

Staphylococcus aureus - genetics

Rabbits

Mutagenesis, Site-Directed

Mitogens - metabolism

Models, Molecular

Protein Structure, Tertiary - genetics

Spleen - cytology

Protein Binding - immunology

Receptors, Antigen, T-Cell, alpha-beta - genetics

Shock, Septic - microbiology

Enterotoxins - genetics

Animals

Superantigens - chemistry

Mitogens - genetics

Superantigens - genetics

Enterotoxins - metabolism

Amino Acid Substitution - genetics

Staphylococcus aureus - immunology

Superantigens - pharmacology

Enterotoxins - chemistry

Histocompatibility Antigens Class II - genetics

Receptors, Antigen, T-Cell, alpha-beta - metabolism

Enterotoxins - pharmacology

Details

Title: Subtitle: Functional analysis of the TCR binding domain of toxic shock syndrome toxin-1 predicts further diversity in MHC class II/superantigen/TCR ternary complexes
Creators: John K McCormick - Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
Timothy J Tripp
Andrea S Llera
Eric J Sundberg
Martin M Dinges
Roy A Mariuzza
Patrick M Schlievert
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.171(3), pp.1385-1392
DOI: 10.4049/jimmunol.171.3.1385
PMID: 12874229
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI36900 / NIAID NIH HHS AI42937 / NIAID NIH HHS AI22159 / NIAID NIH HHS
Language: English
Date published: 08/01/2003
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001108202771

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