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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

Modelling of the TCR-SEE-(MHC)2 quaternary complex.(A) Sequence alignment of SEE with SEA, SEB, SEH and SEI, displaying the conservation of both MHC binding sites in SEE, made using ClustalW2 [84, 85]. The N-terminal binding site to the MHC α-chain is marked in green and the C-terminal binding site to the MHC β-chain is marked in purple. (B) The initial model of TCR-SEE-(MHC)2. The TCR is shown in purple and blue (TCRα and TCRβ respectively), the SEE in beige, and MHC molecules in green. (C) The final model of TCR-SEE-(MHC)2. (D) The TCR-SEB-MHC structure, with SEB shown in orange.
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pone.0131988.g005: Modelling of the TCR-SEE-(MHC)2 quaternary complex.(A) Sequence alignment of SEE with SEA, SEB, SEH and SEI, displaying the conservation of both MHC binding sites in SEE, made using ClustalW2 [84, 85]. The N-terminal binding site to the MHC α-chain is marked in green and the C-terminal binding site to the MHC β-chain is marked in purple. (B) The initial model of TCR-SEE-(MHC)2. The TCR is shown in purple and blue (TCRα and TCRβ respectively), the SEE in beige, and MHC molecules in green. (C) The final model of TCR-SEE-(MHC)2. (D) The TCR-SEB-MHC structure, with SEB shown in orange.

Mentions: As mentioned, the group III SAgs is distinguished by one TCR binding site and two MHC class II binding sites [12–15]. One site is between the N-terminal domain of the SAg and the α-chain of MHC utilizing Lys39 on MHC class II [15], and the other is in the C-terminal domain of the SAg to the β-chain of MHC, bridged by a zinc ion utilizing His81 on MHC class II [14]. In contrast, the group II SAgs, such as SEB, only has one TCR and one MHC class II binding site, to the α-chain of MHC [37]. Due to the similarity between SEE and SEA in their dependence of His81 and Lys39 for MHC binding, and the sequential conservation of both the N-terminal and zinc dependent C-terminal MHC class II binding sites (Fig 5A), it is likely that SEE, as SEA, is able to cross-link two MHC class II molecules, as also previously been suggested (Fig 5B) [15, 77, 78]. A zinc ion is visible in the SEE-TCR structure presented here, coordinated by residues His187s, His225s, and Asp227s, as well as Asp225b from the β-chain of a symmetry-related TCR, due to crystal packing. The three equivalent residues in SEA, SEI and two in SEH are known to coordinate the zinc ion in these SAgs [42, 79, 80] and are crucial for biological activity [14, 81]. Since the zinc binding site to MHC is conserved (Fig 5A), it is likely that SEE will engage the β-chain of MHC, using its C-terminal domain, in a manner similar to what has been observed for SEI [42]. In addition, many of the known MHC-coordinating residues in the N-terminal MHC binding site (to the α-chain) are conserved between SEE, SEA and SEB (Fig 5A).


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)

Modelling of the TCR-SEE-(MHC)2 quaternary complex.(A) Sequence alignment of SEE with SEA, SEB, SEH and SEI, displaying the conservation of both MHC binding sites in SEE, made using ClustalW2 [84, 85]. The N-terminal binding site to the MHC α-chain is marked in green and the C-terminal binding site to the MHC β-chain is marked in purple. (B) The initial model of TCR-SEE-(MHC)2. The TCR is shown in purple and blue (TCRα and TCRβ respectively), the SEE in beige, and MHC molecules in green. (C) The final model of TCR-SEE-(MHC)2. (D) The TCR-SEB-MHC structure, with SEB shown in orange.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131988.g005: Modelling of the TCR-SEE-(MHC)2 quaternary complex.(A) Sequence alignment of SEE with SEA, SEB, SEH and SEI, displaying the conservation of both MHC binding sites in SEE, made using ClustalW2 [84, 85]. The N-terminal binding site to the MHC α-chain is marked in green and the C-terminal binding site to the MHC β-chain is marked in purple. (B) The initial model of TCR-SEE-(MHC)2. The TCR is shown in purple and blue (TCRα and TCRβ respectively), the SEE in beige, and MHC molecules in green. (C) The final model of TCR-SEE-(MHC)2. (D) The TCR-SEB-MHC structure, with SEB shown in orange.
Mentions: As mentioned, the group III SAgs is distinguished by one TCR binding site and two MHC class II binding sites [12–15]. One site is between the N-terminal domain of the SAg and the α-chain of MHC utilizing Lys39 on MHC class II [15], and the other is in the C-terminal domain of the SAg to the β-chain of MHC, bridged by a zinc ion utilizing His81 on MHC class II [14]. In contrast, the group II SAgs, such as SEB, only has one TCR and one MHC class II binding site, to the α-chain of MHC [37]. Due to the similarity between SEE and SEA in their dependence of His81 and Lys39 for MHC binding, and the sequential conservation of both the N-terminal and zinc dependent C-terminal MHC class II binding sites (Fig 5A), it is likely that SEE, as SEA, is able to cross-link two MHC class II molecules, as also previously been suggested (Fig 5B) [15, 77, 78]. A zinc ion is visible in the SEE-TCR structure presented here, coordinated by residues His187s, His225s, and Asp227s, as well as Asp225b from the β-chain of a symmetry-related TCR, due to crystal packing. The three equivalent residues in SEA, SEI and two in SEH are known to coordinate the zinc ion in these SAgs [42, 79, 80] and are crucial for biological activity [14, 81]. Since the zinc binding site to MHC is conserved (Fig 5A), it is likely that SEE will engage the β-chain of MHC, using its C-terminal domain, in a manner similar to what has been observed for SEI [42]. In addition, many of the known MHC-coordinating residues in the N-terminal MHC binding site (to the α-chain) are conserved between SEE, SEA and SEB (Fig 5A).

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