Structural and kinetic basis for low affinity cross-reactivity in T cell allorecognition
✍ Scribed by Annick Guimezanes; Félix Montero-Julian; Anne-Marie Schmitt-Verhulst
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 254 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
The alloreactive BM3.3TCR interacts with high affinity with H‐2K^b^ loaded with the endogenous peptide pBM1 (INFDFNTI), and shows low affinity cross‐reactivity for H‐2K^b^ loadedwith a viral peptide VSV8 (RGYVYQGL), CTL activity requiring 10^3^‐fold higher peptide concentration and being highly sensitive to inhibition by anti‐CD8 monoclonal antibody. VSV8 peptides substituted with pBM1/TCR contact residues (N6 and T7) retained low affinity characteristics and among pBM1 peptides substituted with residues Q6 and/or G7 present in VSV8, only pBM1(G7) was recognized, albeit with characteristics akin to those of VSV8. Despite the difference in K~D~ values and the faster dissociation rate of multimeric VSV8/H‐2K^b^ as compared to pBM1/H‐2K^b^ complexes, similar TCR occupancy could be achieved with both multimers either at 4 or 37°C. Only TCR engagement with pBM1/H‐2K^b^, however, resulted in early (Ca^2+^ flux) and late(CD69 expression) activation events in naive BM3.3TCR CD8 T cells. CD8 coreceptor, essential for binding of the weak agonists, was dispensable for binding of pBM1/H‐2K^b^ multimers and their induction of signaling in naive T cells. Hence, high number of TCR and coreceptor engagement by weak agonists fail to substitute for strong agonist TCR engagement that can be coreceptor‐independent and involve a limited number of TCR.