Identification of MHC Class II-Associated Peptides That Promote the Presentation of Toxic Shock Syndrome Toxin-1 to T Cells

Abstract

Previous studies have shown that the DM-deficient cell line, T2-I-Ab, is very inefficient at presenting toxic shock syndrome toxin 1 (TSST-1) to T cells, suggesting that I-Ab-associated peptides play an essential role in the presentation of this superantigen. Consistent with this, the loading of an I-Ab-binding peptide, staphylococcal enterotoxin B 121–136, onto T2-I-Ab cells enhanced TSST-1 presentation >1000-fold. However, despite extensive screening, no other peptides have been identified that significantly promote TSST-1 presentation. In addition, the peptide effect on TSST-1 presentation has been demonstrated only in the context of the tumor cell line T2-I-Ab. Here we show that peptides that do not promote TSST-1 presentation can be converted into “promoting” peptides by the progressive truncation of C-terminal residues. These studies result in the identification of two peptides derived from IgGV heavy chain and I-Eα proteins that are extremely strong promoters of TSST-1 presentation (47,500- and 12,000-fold, respectively). We have also developed a system to examine the role of MHC class II-associated peptides in superantigen presentation using splenic APC taken directly ex vivo. The data confirmed that the length of the MHC class II-bound peptide plays a critical role in the presentation of TSST-1 by splenic APC and showed that different subpopulations of APC are equally peptide dependent in TSST-1 presentation. Finally, we demonstrated that the presentation of staphylococcal enterotoxin A, like TSST-1, is peptide dependent, whereas staphylococcal enterotoxin B presentation is peptide independent.

MMTV Superantigens Coerce an Unconventional Topology between the TCR and MHC Class II

“…Future studies will address this issue by characterizing the impact of a larger panel of N-terminal extensions linked to various core peptides. Nevertheless, knowing the profound effect of PFRs on canonical and toxic shock syndrome toxin-1 T cell responses (39,68,69), and that DM favors the binding of peptides that tightly fit the groove, our findings point to N-terminal peptide trimming as a potentially important determinant for vSAG presentation (40,70). These results explain why DM-deficient cells, either murine or human, are unable to present vSAG7, as they are predominantly charged with CLIP peptide bearing a 4-to 6-aa extension (34,45,71).…”

“…Similarly, presentation of these SAGs by cells from H2-DM-deficient mice was inefficient (37)(38)(39). DM edits the peptide repertoire by exchanging CLIP for a variety of peptides with better kinetic stability (40).…”

Decreased IL‐10 production by psoriatic peripheral blood mononuclear cells stimulated with streptococcal superantigen

“…However, the following question still remains unanswered why psoriatic PBMCs are hyporesponsive in IL‐10 production only to CAP stimulation. Recently, it has becomes clear that there is a difference among superantigens in the dependency on MHC class II‐associated peptides to stimulate T cells (31). In addition, in our previous paper, we have demonstrated that, although both CAP and SEE stimulated Vβ8+ T cells, psoriatic patients were hyporesponsive only for CAP, which suggests that the signals induced by CAP and SEE are apparently different even in Vβ8+ T cells.…”

Streptococcal Superantigens

“…Further evidence was provided when the SPE-C-HLA-DR2a structure revealed extensive interaction of the bound peptide [66]. This raises the possibility that certain bound peptides could enhance the potency of the SAg by promoting high-affinity, but low-density binding to MHC class II [67,68]. This mechanism might be important to avoid T cell apoptosis through supraoptimal signalling caused by high ligand densities.…”