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J. Exp. Med.,
Volume 188, Number 10, November 16, 1998 1867-1874
By
From the Department of Laboratory Medicine and Pathology and Center for Immunology, University
of Minnesota, Minneapolis, Minnesota 55455
During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide-major histocompatibility complex (MHC) complexes that bind the T cell receptor with
low affinity will promote positive selection while those with high affinity will result in negative
selection. Upon thymocyte maturation, such low affinity self-peptide-MHC ligands no longer
provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes
are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb
stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would
potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide-MHC ligands.
Remarkably, the preselection thymocytes were more responsive than mature T cells when
stimulated with low affinity peptide variants, while both populations responded equally well to
the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide-MHC complexes.
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