Structure of Staphylococcal Enterotoxin E in Complex with TCR Defines the Role of TCR Loop Positioning in Superantigen Recognition.

Karin E J Rödström,Paulina Regenthal,Karin Lindkvist-Petersson,Wenqing Xu

doi:10.1371/journal.pone.0131988

Abstract

T cells are crucial players in cell-mediated immunity. The specificity of their receptor, the T cell receptor (TCR), is central for the immune system to distinguish foreign from host antigens. Superantigens are bacterial toxins capable of inducing a toxic immune response by cross-linking the TCR and the major histocompatibility complex (MHC) class II and circumventing the antigen specificity. Here, we present the structure of staphylococcal enterotoxin E (SEE) in complex with a human T cell receptor, as well as the unligated T cell receptor structure. There are clear structural changes in the TCR loops upon superantigen binding. In particular, the HV4 loop moves to circumvent steric clashes upon complex formation. In addition, a predicted ternary model of SEE in complex with both TCR and MHC class II displays intermolecular contacts between the TCR α-chain and the MHC, suggesting that the TCR α-chain is of importance for complex formation.

Highlights

Tcell activation is a fundamental event in the immune response, which requires T cell receptor (TCR) recognition of a peptide presented by the major histocompatibility complex (MHC) [1]
The superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are divided into five evolutionary groups (I-V), depending on sequence similarity, and each group has structurally diverse ways of engaging TCR and MHC class II [10]
The structure presented here features staphylococcal enterotoxin E in complex with a T cell receptor. This structure, in combination with the unligated TCR structure, shows that flexibility of the HV4 loop is of importance for Staphylococcal enterotoxin E (SEE) binding to TCR

Summary

Introduction

Tcell activation is a fundamental event in the immune response, which requires T cell receptor (TCR) recognition of a peptide presented by the major histocompatibility complex (MHC) [1]. Superantigens are immune stimulatory toxins that bind directly to TCR and MHC as unprocessed proteins, and prevent the TCR from recognizing the peptide presented by MHC [6,7,8]. By this cross-linking event, superantigens are capable of evoking an immune response of large proportions, resulting in host disease [9].

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Results

Conclusion