Titre
Discrepancy between in vitro measurable and in vivo virus neutralizing cytotoxic T cell reactivities. Low T cell receptor specificity and avidity sufficient for in vitro proliferation or cytotoxicity to peptide-coated target cells but not for in vivo protection
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Speiser, D. E.
Auteure/Auteur
Kyburz, D.
Auteure/Auteur
Stubi, U.
Auteure/Auteur
Hengartner, H.
Auteure/Auteur
Zinkernagel, R. M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
1992-08
Volume
149
Numéro
3
Première page
972
Dernière page/numéro d’article
80
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug 1
Research Support, Non-U.S. Gov't --- Old month value: Aug 1
Résumé
The TCR-alpha beta of CTL recognize peptide Ag in association with MHC class I molecules. TCR binding should be highly specific to guarantee pathogen specificity and to avoid self-reactivity. Therefore, the in vivo relevance of T cells exhibiting cross-reactivities in vitro and the respective role of the TCR affinities involved are not clear. To analyze high and low avidity T cell activities both in vitro and in vivo, we investigated primary and clonal CTL responses specific for the lymphocytic choriomeningitis virus nucleoprotein 118-126 epitope in association with the two closely related H-2Ld or H-2Lq molecules. As expected, we found highly specific class I-allele-restricted CTL responses when antiviral protection or immunopathology in vivo and lysis of virus infected target cells in vitro were analyzed. In contrast, the CTL were MHC crossreactive and thus considerably less discriminatory against targets expressing high MHC-peptide densities and in proliferation assays. The data show that relatively high TCR avidities are required for virus neutralization in vivo, in contrast to in vitro analyses of peptide-coated target cells or proliferative T cell responses that may engage TCR of low avidity and broad specificity and therefore may not reflect biologically relevant TCR avidities.
Sujets
PID Serval
serval:BIB_E0AE574F0704
PMID
Date de création
2008-01-28T10:32:46.866Z
Date de création dans IRIS
2025-05-20T22:51:51Z