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 language | English (US) |
|---|---|
| Pages (from-to) | 187-195 |
| Number of pages | 9 |
| Journal | Nature immunology |
| Volume | 17 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2016 |
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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 journal › Article
}
TY - JOUR
T1 - Tolerance is established in polyclonal CD4 + T cells by distinct mechanisms, according to self-peptide expression patterns
AU - Malhotra, Deepali
AU - Linehan, Jonathan L.
AU - Dileepan, Thamotharampillai
AU - Lee, You Jeong
AU - Purtha, Whitney E.
AU - Lu, Jennifer V.
AU - Nelson, Ryan W.
AU - Fife, Brian T.
AU - Orr, Harry T.
AU - Anderson, Mark S.
AU - Hogquist, Kristin A.
AU - Jenkins, Marc K.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84955100080&partnerID=8YFLogxK
U2 - 10.1038/ni.3327
DO - 10.1038/ni.3327
M3 - Article
C2 - 26726812
AN - SCOPUS:84955100080
VL - 17
SP - 187
EP - 195
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 2
ER -