Preselection thymocytes are more sensitive to T cell receptor stimulation than mature T cells.
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.
Davey
G M
GM
Department of Laboratory Medicine and Pathology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Schober
S L
SL
Endrizzi
B T
BT
Dutcher
A K
AK
Jameson
S C
SC
Hogquist
K A
KA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005434:Flow Cytometry; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin; D002118:Calcium