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The Journal of Immunology, 2001, 166: 6514-6522.
Copyright © 2001 by The American Association of Immunologists

Identification of MHC Class II-Associated Peptides That Promote the Presentation of Toxic Shock Syndrome Toxin-1 to T Cells1

Robert J. Hogan2,*, Josine VanBeek2,{dagger}, Dana R. Broussard{dagger}, Sherri L. Surman{dagger} and David L. Woodland3,*

* Trudeau Institute, Saranac Lake, NY 12983; and {dagger} Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105

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-E{alpha} 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.




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