T Cell Receptor Antagonist Peptides Induce Positive Selection

University of Washington Seattle, Seattle, Washington, United States
Cell (Impact Factor: 32.24). 02/1994; 76(1):17-27. DOI: 10.1016/0092-8674(94)90169-4
Source: PubMed


We have used organ culture of fetal thymic lobes from T cell receptor (TCR) transgenic beta 2M(-/-) mice to study the role of peptides in positive selection. The TCR used was from a CD8+ T cell specific for ovalbumin 257-264 in the context of Kb. Several peptides with the ability to induce positive selection were identified. These peptide-selected thymocytes have the same phenotype as mature CD8+ T cells and can respond to antigen. Those peptides with the ability to induce positive selection were all variants of the antigenic peptide and were identified as TCR antagonist peptides for this receptor. One peptide tested, E1, induced positive selection on the beta 2M(-/-) background but negative selection on the beta 2M(+/-) background. These results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.

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    • "More recently, Huang et al. [38] demonstrated that OVA complexed inside hollow yeast glucan shells was processed by BMDC and activated both CD4 and CD8 T cells as measured by tritiated thymidine incorporation. To see if a similar cross-presentation of OVA peptides to CD8 T cells was possible with MG:OVA, we used splenocytes from OT-1 mice where most of the CD8 T cells have a receptor specific for the OVA 257–264 peptide [33]. We found that BMDC treated with MG:OVA activated naïve CD8+ cells not only in terms of increased CD25 expression, but also in increased expression of a functional cytotoxic molecule, Granzyme B [35]. "
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    • "C57BL/6 (BL6) mice were purchased from The Jackson Laboratory (Bar Harbor, ME) and bred in our facility (Roswell Park Cancer Institute, RPCI) under an approved Animal Committee protocol. OT-I (H-2K b restricted, anti-OVA TCR transgenic) mice[46]on Rag2 −/− background were also bred at RPCI. Lag3 −/− mice[47]were a kind gift from Dario Vignali (St. "
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    • "Failure to kill target cells enhances cytokine secretion by CTLs/NK cells We first generated antigen-restricted CTLs from transgenic C57BL/6.OTI (OTI) mice (Strasser et al., 1990a; Hogquist et al., 1994 "
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