title: Self-recognition drives the preferential accumulation of promiscuous CD4(+) T-cells in aged mice.
abstract: T-cell recognition of self and foreign peptide antigens presented in major histocompatibility complex molecules (pMHC) is essential for life-long immunity. How the ability of the CD4(+) T-cell compartment to bind self- and foreign-pMHC changes over the lifespan remains a fundamental aspect of T-cell biology that is largely unexplored. We report that, while old mice (18-22 months) contain fewer CD4(+) T-cells compared with adults (8-12 weeks), those that remain have a higher intrinsic affinity for self-pMHC, as measured by CD5 expression. Old mice also have more cells that bind individual or multiple distinct foreign-pMHCs, and the fold increase in pMHC-binding populations is directly related to their CD5 levels. These data demonstrate that the CD4(+) T-cell compartment preferentially accumulates promiscuous constituents with age as a consequence of higher affinity T-cell receptor interactions with self-pMHC.
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, United States.
authors.forename: Neha R
authors.initials: NR
authors.lastname: Deshpande
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, United States.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Parrish
authors.affiliation: Department of Immunobiology, University of Arizona College of Medicine, Tucson, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kuhns
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000032:analysis; D051379:Mice; D017634:Self Tolerance
chemical_list: D001324:Autoantigens; D018956:CD5 Antigens; C526836:Cd5 protein, mouse
keywords: CD4; CD5; T cell; aging; class II MHC; immunology; mouse; repertoire