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A TCR Binds to Antagonist Ligands with Lower Affinities and Faster Dissociation Rates Than to Agonists
Open accessAbstract
T lymphocyte activation is mediated by the interaction of specific TCR with antigenic peptides bound to MHC molecules. Single amino acid substitutions are often capable of changing the effect of a peptide from stimulatory to antagonistic. Using surface plasmon resonance, we have analyzed the interaction between a complex consisting of variants of the MCC peptide bound to a mouse class II MHC (Ek) and a specific TCR. Using both an improved direct binding method as well as a novel inhibition assay, we show that the affinities of three different antagonist peptide-Ek complexes are approximately 10-50 times lower than that of the wildtype MCC-Ek complex for the TCR, largely due to an increased off-rate. These results suggest that the biological effects of peptide antagonists and partial agonists may be largely based on kinetic parameters.
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Citations
Cites
Yung-Chi, C., & Prusoff, W. H. (1973) · Biochemical Pharmacology · doi:10.1016/0006-2952(73)90196-2 · Cited by 12,922
Cited by
Porgador, A., Yewdell, J. W., Deng, Y., Bennink, J. R., & Germain, R. N. (1997) · Immunity · doi:10.1016/s1074-7613(00)80447-1 · Cited by 669
Dustin, M. L. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0161 · Cited by 502
TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways
Štefanová, I., Hemmer, B., Vergelli, M., Martin, R., Biddison, W. E., & Germain, R. N. (2003) · Nature Immunology · doi:10.1038/ni895 · Cited by 465
Organizing MHC Class II presentation
Fooksman, D. R. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00158 · Cited by 41
Counterselection against Dμ Is Mediated through Immunoglobulin (Ig)α-Igβ
Gong, S., Sanchez, M., & Nussenzweig, M. C. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.6.2079 · Cited by 16
Metadata
- Authors
- Lyons, D. S., Lieberman, S. A., Hampl, J., Boniface, J. J., Chien, Y.-H., Berg, L. J., & Davis, M. M.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1996-07
- Volume
- 5
- Issue
- 1
- Pages
- 53-61
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1992699522
- Cited by
- 418
- References
- 1
- FWCI
- 19.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
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