TcellhomeostasiscommonlyreferstothemaintenanceofrelativelystableTcellnumbersintheperipherallymphoidorgans.AmongthelargenumbersofTcellsintheperiphery,Tcellsexhibitstructuralpersity,I.e.,theexpressionofaperserepertoireofTcellreceptors(TCRs),andfunctionalpersity,I.e.,thepresenceofTcellsatna(I)ve,effector,andmemorydevelopmentalstages.AlthoughthehomeostasisofTcellnumbershasbeenextensivelystudied,investigationofthemechanismsunderlyingthemaintenanceofstructuralandfunctionalpersityofTcellsisstillatanearlystage.ThefundamentalfeaturethroughoutTcelldevelopmentistheinteractionbetweentheTCRandeitherselforforeignpeptidesinassociationwithMHCmolecules.Inthisreview,wepresentevidenceshowingthathomeostasisofTcellnumberandpersityismediatedthroughcompetitionforlimitingresources.ThenumberofTcellsismaintainedthroughcompetitionforlimitingcytokines,whereasthepersityofTcellsismaintainedbycompetitionforself-peptide-MHCcomplexes.Inotherwords,persityoftheself-peptiderepertoirelimitsthestructural(TCR)persityofaTcellpopulation.Wespeculatethatcognatelowaffinityself-peptides,actingasweakagonistsandantagonists,regulatethehomeostasisofTcellpersitywhereasnon-cognateornullpeptideswhichareextremelyabundantforanygivenTCR,maycontributetothehomeostasisofTcellnumberbyprovidingsurvivalsignals.Moreover,self-peptidesandcytokinesmayformspecializednichesfortheregulationofTcellhomeostasis.
