Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 5, Pages 2952-2960Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.5.2952
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Funding
- NCI NIH HHS [CA 92368] Funding Source: Medline
- NIGMS NIH HHS [GM 67143] Funding Source: Medline
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Binding of peptide/MHC (pMHC) complexes by TCR initiates T cell activation. Despite long interest, the exact relationship between the biochemistry of TCR/pMHC interaction (particularly TCR affinity or ligand off-rate) and T cell responses remains unresolved, because the number of complexes examined in each independent system has been too small to draw a definitive conclusion. To test the current models of T cell activation, we have analyzed the interactions between the mouse P14 TCR and a set of altered peptides based on the lymphocytic choriomeningitis virus epitope gp33-41 sequence bound to mouse class I MHC D-b. pMHC binding, TCR-binding characteristics, CD8(+) T cell cytotoxicity, and IFN-gamma production were measured for the peptides. We found affinity correlated well with both cytotoxicity and IFN-gamma production. In contrast, no correlation was observed between any kinetic parameter of TCR-pMHC interaction and cytotoxicity or IFN-gamma production. This study strongly argues for an affinity threshold model of T cell activation.
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