Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors.
Naturally arising CD25+ CD4+ regulatory T cells (TR) play an important role in the prevention of autoimmunity. TCR specificity is thought to play a critical role in TR development and function, but the repertoire and specificity of TR TCRs remain largely unknown. We find by sequencing of TRAV14 (Valpha2) TCRalpha chains associated with a transgenic TCRbeta chain that the TRand CD25- CD4+ TCR repertoires are similarly diverse, yet only partially overlapping. Retroviral expression of TCRalpha genes in TCR transgenic RAG-deficient T cells revealed that a high frequency of TCRs derived from CD25+ but not CD25- CD4+ T cells confers the ability to rapidly expand upon transfer into a lymphopenic host. Thus, these data show that a large proportion of naturally arising TR have substantially more efficient interactions with MHC class II bound peptides from the peripheral self than CD25- T cells.
Department of Medicine, Division of Rheumatology, University of Washington, Seattle, Washington 98195, USA.
Chyi-Song
CS
Hsieh
Yuqiong
Y
Liang
Aaron J
AJ
Tyznik
Steven G
SG
Self
Denny
D
Liggitt
Alexander Y
AY
Rudensky
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D051379:Mice; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology* / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D001324:Autoantigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2