title: T cell receptor cross-reactivity between similar foreign and self peptides influences naive cell population size and autoimmunity.
abstract: T cell receptor (TCR) cross-reactivity between major histocompatibility complex II (MHCII)-binding self and foreign peptides could influence the naive CD4(+) T cell repertoire and autoimmunity. We found that nonamer peptides that bind to the same MHCII molecule only need to share five amino acids to cross-react on the same TCR. This property was biologically relevant because systemic expression of a self peptide reduced the size of a naive cell population specific for a related foreign peptide by deletion of cells with cross-reactive TCRs. Reciprocally, an incompletely deleted naive T cell population specific for a tissue-restricted self peptide could be triggered by related microbial peptides to cause autoimmunity. Thus, TCR cross-reactivity between similar self and foreign peptides can reduce the size of certain foreign peptide-specific T cell populations and might allow T cell populations specific for tissue-restricted self peptides to cause autoimmunity after infection.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Nelson
authors.forename: Daniel
authors.initials: D
authors.lastname: Beisang
authors.forename: Noah J
authors.initials: NJ
authors.lastname: Tubo
authors.forename: Thamotharampillai
authors.initials: T
authors.lastname: Dileepan
authors.forename: Darin L
authors.initials: DL
authors.lastname: Wiesner
authors.forename: Kirsten
authors.initials: K
authors.lastname: Nielsen
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Klein
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Kotov
authors.forename: Justin A
authors.initials: JA
authors.lastname: Spanier
authors.forename: Brian T
authors.initials: BT
authors.lastname: Fife
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.forename: Marc K
authors.initials: MK
authors.lastname: Jenkins
mesh_terms: D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D060966:Clonal Selection, Antigen-Mediated; D003429:Cross Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology*; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D040901:Proteomics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell