Tolerance is established in polyclonal CD4 + T cells by distinct mechanisms, according to self-peptide expression patterns

Deepali Malhotra, Jonathan L. Linehan, Thamotharampillai Dileepan, You Jeong Lee, Whitney E. Purtha, Jennifer V. Lu, Ryan W. Nelson, Brian T. Fife, Harry T. Orr, Mark S. Anderson, Kristin A. Hogquist, Marc K. Jenkins

Research output: Contribution to journalArticle

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Abstract

Studies of repertoires of mouse monoclonal CD4 + T cells have revealed several mechanisms of self-tolerance; however, which mechanisms operate in normal repertoires is unclear. Here we studied polyclonal CD4 + T cells specific for green fluorescent protein expressed in various organs, which allowed us to determine the effects of specific expression patterns on the same epitope-specific T cells. Peptides presented uniformly by thymic antigen-presenting cells were tolerated by clonal deletion, whereas peptides excluded from the thymus were ignored. Peptides with limited thymic expression induced partial clonal deletion and impaired effector T cell potential but enhanced regulatory T cell potential. These mechanisms were also active for T cell populations specific for endogenously expressed self antigens. Thus, the immunotolerance of polyclonal CD4 + T cells was maintained by distinct mechanisms, according to self-peptide expression patterns.

Original languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalNature immunology
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2016

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T-Lymphocytes
Peptides
Clonal Deletion
Self Tolerance
T-Lymphocyte Epitopes
Autoantigens
Antigen-Presenting Cells
Regulatory T-Lymphocytes
Green Fluorescent Proteins
Thymus Gland
Population

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Tolerance is established in polyclonal CD4 + T cells by distinct mechanisms, according to self-peptide expression patterns. / Malhotra, Deepali; Linehan, Jonathan L.; Dileepan, Thamotharampillai; Lee, You Jeong; Purtha, Whitney E.; Lu, Jennifer V.; Nelson, Ryan W.; Fife, Brian T.; Orr, Harry T.; Anderson, Mark S.; Hogquist, Kristin A.; Jenkins, Marc K.

In: Nature immunology, Vol. 17, No. 2, 01.02.2016, p. 187-195.

Research output: Contribution to journalArticle

Malhotra, Deepali ; Linehan, Jonathan L. ; Dileepan, Thamotharampillai ; Lee, You Jeong ; Purtha, Whitney E. ; Lu, Jennifer V. ; Nelson, Ryan W. ; Fife, Brian T. ; Orr, Harry T. ; Anderson, Mark S. ; Hogquist, Kristin A. ; Jenkins, Marc K. / Tolerance is established in polyclonal CD4 + T cells by distinct mechanisms, according to self-peptide expression patterns. In: Nature immunology. 2016 ; Vol. 17, No. 2. pp. 187-195.
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