T cells down-modulate peptide-MHC complexes on APCs in vivo.
T cells compete in the response to antigen in vivo and this competition may drive the affinity maturation of a secondary T cell response. Here we show that high-affinity T cells out-competed lower affinity T cells during a response to antigenic challenge in vivo. Although competition between T cells specific for different peptide-major histocompatibility complexes (MHC) occurred, it was less efficient than competition between T cells of the same peptide-MHC specificity. In addition, high-affinity T cells efficiently induced antigen loss from the surface of antigen-presenting cells. Thus T cells that responded to the same peptide-MHC competed with each other by lowering the amount of ligand with which the cells could react. As a result, the activation of high-affinity cells was favored. This provides a mechanism for the affinity maturation of a secondary T cell response.
Kedl
Ross M
RM
Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA. rmkedl@mmm.com
Schaefer
Brian C
BC
Kappler
John W
JW
Marrack
Philippa
P
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004527:Egg Proteins / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D006023:Glycoproteins / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D007156:Immunologic Memory; D018655:Lymphocyte Count; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014764:Viral Proteins / Q000276:immunology*
D000941:Antigens; D000956:Antigens, Viral; D004527:Egg Proteins; D006023:Glycoproteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D046911:Macromolecular Substances; C110366:OVA-8; D009842:Oligopeptides; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; C406862:superagonist SIYR; D010047:Ovalbumin