Dissociation of peripheral T cell responses from thymocyte negative selection by weak agonists supports a spare receptor model of T cell activation.
We have focused on stability of the peptide-MHC complex as a determining factor of ligand potency for thymocytes and peripheral CD4+ T cell responses. MHC variant peptides that have low affinities and fast dissociation rates are different in that they stimulate proliferation and cytolysis of mature T cells (classifying the variant peptides as weak agonists) but do not induce thymocyte negative selection. The MHC variant weak agonists require significant receptor reserve, because decreasing the level of T cell receptor on mature T cells blocks the proliferative response. These results demonstrate that peripheral T cells are more sensitive to MHC variant ligands by virtue of increased T cell receptor expression; in addition, the data support a T cell model of the spare receptor theory.
McNeil
Lisa K
LK
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Evavold
Brian D
BD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006649:Histocompatibility Antigens / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D010455:Peptides / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*
D006649:Histocompatibility Antigens; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell