Strong similarities in antigen fine specificity among DRB1* 1302-restricted tetanus toxin tt830-843-specific TCRs in spite of highly heterogeneous CDR3

Détails

ID Serval
serval:BIB_3547AA98E23B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Strong similarities in antigen fine specificity among DRB1* 1302-restricted tetanus toxin tt830-843-specific TCRs in spite of highly heterogeneous CDR3
Périodique
Journal of Immunology
Auteur⸱e⸱s
Boitel  B., Blank  U., Mege  D., Corradin  G., Sidney  J., Sette  A., Acuto  O.
ISSN
0022-1767 (Print)
Statut éditorial
Publié
Date de publication
04/1995
Volume
154
Numéro
7
Pages
3245-55
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr 1
Résumé
We investigated the Ag fine specificity of four TCRs that shared the same V beta segment but used V alpha s of three different subfamilies and displayed highly heterogeneous alpha and beta CDR3. The TCRs recognized the tetanus toxin tt830-843 (QYIKANSKFIGITE) epitope presented by DRB1*1302. By using a large panel of monosubstituted peptide analogues, we first defined the requirements for tt830-843 binding to DRB1*1302. We found that three residues, I832, N835, and G840, were critical for the interaction with DRB1*1302. Residues potentially contacted by the four TCRs were functionally defined by measuring the IL-2 response to the analogues. Except for the first and the last three residues, as well as I832 and G340, all of the others appeared to provide contacts with the four TCRs, indicating a considerable overlapping in the way these TCRs interact with the peptide. More importantly, and contrary to expectations, the two TCRs expressing the same V alpha/V beta germ-line segments showed a strikingly similar reactivity toward nearly all substitutions; moreover, more pronounced differences were observed when comparing TCRs using different V alpha segments. These results indicate that TCRs with entirely distinct CDR3s in the context of conserved V segments may not differ substantially in the way they recognize the ligand, and may provide new insights into understanding the formation of TCR/peptide/MHC ternary complexes. During these studies, we noticed that analogues with nonconservative substitutions at I832, which bound very unstably to DRB1*1302, could effectively stimulate T cells, suggesting a role of the TCR in contributing toward stabilization of peptide binding.
Mots-clé
Amino Acid Sequence Epitopes/immunology HLA-DR Antigens/genetics/*immunology Humans Interleukin-2/physiology Molecular Sequence Data Peptide Fragments/immunology Protein Binding/immunology Receptors, Antigen, T-Cell, alpha-beta/*chemistry/*immunology Tetanus Toxin/chemistry/*immunology
Pubmed
Web of science
Création de la notice
24/01/2008 14:55
Dernière modification de la notice
20/08/2019 13:22
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