Fine structural variations of alphabetaTCRs selected by vaccination with natural versus altered self-antigen in melanoma patients.

Details

Serval ID
serval:BIB_0B1196ECB9E4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fine structural variations of alphabetaTCRs selected by vaccination with natural versus altered self-antigen in melanoma patients.
Journal
Journal of Immunology
Author(s)
Wieckowski S., Baumgaertner P., Corthesy P., Voelter V., Romero P., Speiser D.E., Rufer N.
ISSN
1550-6606[electronic]
Publication state
Published
Issued date
2009
Volume
183
Number
8
Pages
5397-5406
Language
english
Abstract
Immunotherapy of cancer is often performed with altered "analog" peptide Ags optimized for HLA class I binding, resulting in enhanced immunogenicity, but the induced T cell responses require further evaluation. Recently, we demonstrated fine specificity differences and enhanced recognition of naturally presented Ag by T cells after vaccination with natural Melan-A/MART-1 peptide, as compared with analog peptide. In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A(26-35)-specific CD8 T cells derived from both cohorts of patients. Although a strong preference for TRAV12-2 segment usage was present in nearly all patients, usage of particular TRAJ gene segments and CDR3alpha composition differed slightly after vaccination with natural vs analog peptide. Moreover, TCR beta-chain repertoires were broader after natural than analog peptide vaccination. In all patients, we observed a marked conservation of the CDR3beta amino acid composition with recurrent sequences centered on a glycyl-leucyl/valyl/alanyl-glycyl motif. In contrast to viral-specific TCR repertoires, such "public" motifs were primarily expressed by nondominant T cell clonotypes, which contrasted with "private" CDR3beta signatures frequently found in T cell clonotypes that dominated repertoires of individual patients. Interestingly, no differences in functional avidity were observed between public and private T cell clonotypes. Collectively, our data indicate that T cell repertoires generated against natural or analog Melan-A peptide exhibited slightly distinct but otherwise overlapping and structurally conserved TCR features, suggesting that the differences in binding affinity/avidity of TCRs toward pMHC observed in the two cohorts of patients are caused by subtle structural TCR variations.
Keywords
T-Cell Responses, Reactive Ctl, In-Vitro, Gene Segment, Influenza-A, Peptide, Receptor, Recognition, Avidity, Virus
Pubmed
Web of science
Open Access
Yes
Create date
03/11/2009 15:10
Last modification date
20/08/2019 12:32
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