| Autor: |
Govern CC; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Paczosa MK, Chakraborty AK, Huseby ES |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2010 May 11; Vol. 107 (19), pp. 8724-9. Date of Electronic Publication: 2010 Apr 26. |
| DOI: |
10.1073/pnas.1000966107 |
| Abstrakt: |
Two contrasting theories have emerged that attempt to describe T-cell ligand potency, one based on the t(1/2) of the interaction and the other based on the equilibrium affinity (K(D)). Here, we have identified and studied an extensive set of T-cell receptor (TCR)-peptide-MHC (pMHC) interactions for CD4(+) cells that have differential K(D)s and kinetics of binding. Our data indicate that ligands with a short t(1/2) can be highly stimulatory if they have fast on-rates. Simple models suggest these fast kinetic ligands are stimulatory because the pMHCs bind and rebind the same TCR several times. Rebinding occurs when the TCR-pMHC on-rate outcompetes TCR-pMHC diffusion within the cell membrane, creating an aggregate t(1/2) (t(a)) that can be significantly longer than a single TCR-pMHC encounter. Accounting for t(a), ligand potency is K(D)-based when ligands have fast on-rates (k(on)) and t(1/2)-dependent when they have slow k(on). Thus, TCR-pMHC k(on) allow high-affinity short t(1/2) ligands to follow a kinetic proofreading model. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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