Naturally occurring low affinity peptide/MHC class I ligands can mediate negative selection and T cell activation.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Naturally occurring low affinity peptide/MHC class I ligands can mediate negative selection and T cell activation.

J Immunol. 1998 Jan 1;160(1):77-86. Unique Identifier : AIDSLINE MED/98211684
Motyka B; Teh HS; Department of Microbiology and Immunology, University of British; Columbia, Vancouver, Canada.

Abstract: The affinity/avidity model for T cell development postulates that ligands with high affinity for the TCR are efficient in negative selection, whereas those with lower affinity/avidity favor positive selection. Using the 2C TCR transgenic model, we evaluated the efficacy of ligands with widely differing affinity for the TCR (3 x 10(3) to 2 x 10(6) M(-1)) in mediating thymocyte deletion. The relative affinities of the 2C TCR for the p2Ca/Ld, dEV-8/Kb, p2Ca-A3/Ld, and p2Ca/Kb ligands are approximately 1000:50:10:1, respectively. Here we show, using an in vitro assay, that the deletion of 2C CD4+ CD8+ thymocytes is mediated not only by p2Ca/Ld, but also by the lower affinity ligands dEV-8/Kb, p2Ca-A3/Ld, and p2Ca/Kb, albeit at relatively higher peptide concentrations. Deletion mediated by low affinity ligands required CD8, whereas high affinity ligand-mediated deletion was CD8 independent. The p2Ca/Kb and dEV-8/Kb ligands are naturally occurring in H-2b mice, and others have shown that p2Ca/Kb can induce the maturation of CD4- CD8+ 2C-TCR(high) thymocytes in fetal thymic organ culture. In this study we showed that in addition to deletion, the p2Ca/Kb and dEV-8/Kb ligands, in the presence of exogenous IL-2, induced mature 2C T cell proliferation, albeit at a lower level than that induced by the high affinity p2Ca/Ld ligand. Thus, the same low affinity ligands that can effect negative selection and, in the case of p2Ca/Kb, the maturation of CD8 single-positive thymocytes can also induce the activation of mature CD8 T cells.

Keywords: *Clonal Deletion *Histocompatibility Antigens Class I/IMMUNOLOGY *Lymphocyte Transformation *Receptors, Antigen, T-Cell, alpha-beta/IMMUNOLOGY

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