The TCR repertoires of regulatory and conventional T cells specific for the same foreign antigen are distinct. J Immunol 2012 Oct 01;189(7):3566-74
Date
08/31/2012Pubmed ID
22933635Pubmed Central ID
PMC3538134DOI
10.4049/jimmunol.1102646Scopus ID
2-s2.0-84866532545 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
The relationship between the TCR repertoires of natural regulatory T cells (nTregs) and conventional CD4(+) T cells (Tconv) capable of responding to the same antigenic epitope is unknown. In this study, we used TCRβ-chain transgenic mice to generate polyclonal nTreg and Tconv populations specific for a foreign Ag. CD4(+) T cells from immunized 3.L2β(+/-) TCRα(+/-) Foxp3(EGFP) mice were restimulated in culture to yield nTregs (EGFP(+)) and Tconv (EGFP(-)) defined by their antigenic reactivity. Relative to Tconv, nTreg expansion was delayed, although a higher proportion of viable nTregs had divided after 72 h. Spectratype analysis revealed that both the nTreg and Tconv responses were different and characterized by skewed distributions of CDR3 lengths. CDR3 sequences from nTregs displayed a divergent pattern of Jα usage, minimal CDR3 overlap (3.4%), and less diversity than did CDR3 sequences derived from Tconv. These data indicate that foreign Ag-specific nTregs and Tconv are clonally distinct and that foreign Ag-specific nTreg populations are constrained by a limited TCR repertoire.
Author List
Relland LM, Williams JB, Relland GN, Haribhai D, Ziegelbauer J, Yassai M, Gorski J, Williams CBAuthor
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCells, Cultured
Epitopes, T-Lymphocyte
Gene Rearrangement, T-Lymphocyte
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell, alpha-beta
T-Lymphocytes
T-Lymphocytes, Regulatory