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

Rödström KE, Regenthal P, Lindkvist-Petersson K - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Lund University, BMC C13, 22 184, Lund, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus

Comparison between the TCR and SEE-TCR structures, aligned with respect to the TRBV domain, in cross-eyed stereo view.(A) Overall differences between the TRBV domains, with the SEE-TCR structure shown in beige and blue and the TCR structure in grey. (B) Close-up of the HV4 loop with residues shown as sticks. (C) Close-up of the HV4 loop shown as Cα trace with 2Fo-Fc electron density maps shown for the two structures, with the SEE-TCR map in blue and the TCR map in grey.
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pone.0131988.g004: Comparison between the TCR and SEE-TCR structures, aligned with respect to the TRBV domain, in cross-eyed stereo view.(A) Overall differences between the TRBV domains, with the SEE-TCR structure shown in beige and blue and the TCR structure in grey. (B) Close-up of the HV4 loop with residues shown as sticks. (C) Close-up of the HV4 loop shown as Cα trace with 2Fo-Fc electron density maps shown for the two structures, with the SEE-TCR map in blue and the TCR map in grey.

Mentions: Differences in the overall structure of the unbound and SEE-bound TCR are small, with RMSD for main chain atoms of 1.3 and 0.91 for TCRα and TCRβ, respectively. This might be due to the introduced disulfide bond between the TRAC and TRBC domains, which potentially could lock the constant domains in certain positions and thus inhibit potential conformational changes upon binding [75]. In the TRAV domain, there are no large changes in the loop conformations. The majority of the loop rearrangements occur in the TRBV domain, with the HV4 loop and CDR1 loops in different positions, whereas CDR2 is only slightly shifted (Fig 4A).


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

Rödström KE, Regenthal P, Lindkvist-Petersson K - PLoS ONE (2015)

Comparison between the TCR and SEE-TCR structures, aligned with respect to the TRBV domain, in cross-eyed stereo view.(A) Overall differences between the TRBV domains, with the SEE-TCR structure shown in beige and blue and the TCR structure in grey. (B) Close-up of the HV4 loop with residues shown as sticks. (C) Close-up of the HV4 loop shown as Cα trace with 2Fo-Fc electron density maps shown for the two structures, with the SEE-TCR map in blue and the TCR map in grey.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492778&req=5

pone.0131988.g004: Comparison between the TCR and SEE-TCR structures, aligned with respect to the TRBV domain, in cross-eyed stereo view.(A) Overall differences between the TRBV domains, with the SEE-TCR structure shown in beige and blue and the TCR structure in grey. (B) Close-up of the HV4 loop with residues shown as sticks. (C) Close-up of the HV4 loop shown as Cα trace with 2Fo-Fc electron density maps shown for the two structures, with the SEE-TCR map in blue and the TCR map in grey.
Mentions: Differences in the overall structure of the unbound and SEE-bound TCR are small, with RMSD for main chain atoms of 1.3 and 0.91 for TCRα and TCRβ, respectively. This might be due to the introduced disulfide bond between the TRAC and TRBC domains, which potentially could lock the constant domains in certain positions and thus inhibit potential conformational changes upon binding [75]. In the TRAV domain, there are no large changes in the loop conformations. The majority of the loop rearrangements occur in the TRBV domain, with the HV4 loop and CDR1 loops in different positions, whereas CDR2 is only slightly shifted (Fig 4A).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Lund University, BMC C13, 22 184, Lund, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus