Abstract
It has been proposed that MHC restriction during thymocyte selection is controlled by coreceptor (CD4 or CD8) sequestration of the signaling molecule Lck. We explored this model as a mechanism for preventing peripheral T cell activation due to non-MHC ligand crossreactivities of TCRs. TCRs that have a range of affinities for a class I MHC ligand were transduced into a T cell hybridoma in the absence or presence of coreceptors. High and intermediate affinity TCRs (KD=17 and 540 nM) did not require CD8 for T cell activity, but CD4 acted as a potent inhibitor of the intermediate affinity TCR. These and other findings support the view that even high-affinity TCR:ligand interactions can be influenced by coreceptor sequestration of Lck. Thus, CD4 and CD8 act as "coreceptor inhibitors" to maintain appropriate TCR-mediated MHC restriction in peripheral T cell activity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7639-7643 |
| Number of pages | 5 |
| Journal | Journal of Immunology |
| Volume | 183 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 15 2009 |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
Cutting edge : Inhibitory effects of CD4 and CD8 on T cell activation induced by high-affinity noncognate ligands. / Chervin, Adam S.; Stone, Jennifer D.; Bowerman, Natalie A.; Kranz, David M.
In: Journal of Immunology, Vol. 183, No. 12, 15.12.2009, p. 7639-7643.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cutting edge
T2 - Inhibitory effects of CD4 and CD8 on T cell activation induced by high-affinity noncognate ligands
AU - Chervin, Adam S.
AU - Stone, Jennifer D.
AU - Bowerman, Natalie A.
AU - Kranz, David M
PY - 2009/12/15
Y1 - 2009/12/15
N2 - It has been proposed that MHC restriction during thymocyte selection is controlled by coreceptor (CD4 or CD8) sequestration of the signaling molecule Lck. We explored this model as a mechanism for preventing peripheral T cell activation due to non-MHC ligand crossreactivities of TCRs. TCRs that have a range of affinities for a class I MHC ligand were transduced into a T cell hybridoma in the absence or presence of coreceptors. High and intermediate affinity TCRs (KD=17 and 540 nM) did not require CD8 for T cell activity, but CD4 acted as a potent inhibitor of the intermediate affinity TCR. These and other findings support the view that even high-affinity TCR:ligand interactions can be influenced by coreceptor sequestration of Lck. Thus, CD4 and CD8 act as "coreceptor inhibitors" to maintain appropriate TCR-mediated MHC restriction in peripheral T cell activity.
AB - It has been proposed that MHC restriction during thymocyte selection is controlled by coreceptor (CD4 or CD8) sequestration of the signaling molecule Lck. We explored this model as a mechanism for preventing peripheral T cell activation due to non-MHC ligand crossreactivities of TCRs. TCRs that have a range of affinities for a class I MHC ligand were transduced into a T cell hybridoma in the absence or presence of coreceptors. High and intermediate affinity TCRs (KD=17 and 540 nM) did not require CD8 for T cell activity, but CD4 acted as a potent inhibitor of the intermediate affinity TCR. These and other findings support the view that even high-affinity TCR:ligand interactions can be influenced by coreceptor sequestration of Lck. Thus, CD4 and CD8 act as "coreceptor inhibitors" to maintain appropriate TCR-mediated MHC restriction in peripheral T cell activity.
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U2 - 10.4049/jimmunol.0901664
DO - 10.4049/jimmunol.0901664
M3 - Article
VL - 183
SP - 7639
EP - 7643
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -