Abstract
In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8 + T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR responsiveness requires positive selection on major histocompatibility complex class I-associated peptides produced by the thymoproteasome, which is specifically expressed in the thymic cortical epithelium. Thymoproteasome-independent positive selection of monoclonal CD8 + T cells results in aberrant TCR responsiveness, homeostatic maintenance and immune responses to infection. These results demonstrate a novel aspect of positive selection, in which TCR affinity for positively selecting peptides produced by thymic epithelium determines the subsequent antigen responsiveness of mature CD8 + T cells in the periphery.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1069-1076 |
| Number of pages | 8 |
| Journal | Nature immunology |
| Volume | 16 |
| Issue number | 10 |
| DOIs | |
| State | Published - Sep 18 2015 |
Fingerprint
Cite this
TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells. / Takada, Kensuke; Van Laethem, Francois; Xing, Yan; Akane, Kazuyuki; Suzuki, Haruhiko; Murata, Shigeo; Tanaka, Keiji; Jameson, Stephen C.; Singer, Alfred; Takahama, Yousuke.
In: Nature immunology, Vol. 16, No. 10, 18.09.2015, p. 1069-1076.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells
AU - Takada, Kensuke
AU - Van Laethem, Francois
AU - Xing, Yan
AU - Akane, Kazuyuki
AU - Suzuki, Haruhiko
AU - Murata, Shigeo
AU - Tanaka, Keiji
AU - Jameson, Stephen C.
AU - Singer, Alfred
AU - Takahama, Yousuke
PY - 2015/9/18
Y1 - 2015/9/18
N2 - In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8 + T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR responsiveness requires positive selection on major histocompatibility complex class I-associated peptides produced by the thymoproteasome, which is specifically expressed in the thymic cortical epithelium. Thymoproteasome-independent positive selection of monoclonal CD8 + T cells results in aberrant TCR responsiveness, homeostatic maintenance and immune responses to infection. These results demonstrate a novel aspect of positive selection, in which TCR affinity for positively selecting peptides produced by thymic epithelium determines the subsequent antigen responsiveness of mature CD8 + T cells in the periphery.
AB - In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8 + T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR responsiveness requires positive selection on major histocompatibility complex class I-associated peptides produced by the thymoproteasome, which is specifically expressed in the thymic cortical epithelium. Thymoproteasome-independent positive selection of monoclonal CD8 + T cells results in aberrant TCR responsiveness, homeostatic maintenance and immune responses to infection. These results demonstrate a novel aspect of positive selection, in which TCR affinity for positively selecting peptides produced by thymic epithelium determines the subsequent antigen responsiveness of mature CD8 + T cells in the periphery.
UR - http://www.scopus.com/inward/record.url?scp=84941995472&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941995472&partnerID=8YFLogxK
U2 - 10.1038/ni.3237
DO - 10.1038/ni.3237
M3 - Article
C2 - 26301566
AN - SCOPUS:84941995472
VL - 16
SP - 1069
EP - 1076
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 10
ER -