The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Single and Dual Amino Acid Substitutions in TCR CDRs Can Enhance Antigen-Specific T Cell Functions
Open accessAbstract
Single and dual amino acid substitution variants were generated in the TCR CDRs of three TCRs that recognize tumor-associated Ags. Substitutions that enhance the reactivity of TCR gene-modified T cells to the cognate Ag complex were identified using a rapid RNA-based transfection system. The screening of a panel of variants of the 1G4 TCR, that recognizes a peptide corresponding to amino acid residues 157–165 of the human cancer testis Ag NY-ESO-1 (SLLMWITQC) in the context of the HLA-A*02 class I allele, resulted in the identification of single and dual CDR3α and CDR2β amino acid substitutions that dramatically enhanced the specific recognition of NY-ESO-1+/HLA-A*02+ tumor cell lines by TCR gene-modified CD4+ T cells. Within this group of improved TCRs, a dual substitution in the 1G4 TCR CDR3α chain was identified that enhanced Ag-specific reactivity in gene-modified CD4+ and CD8+ T cells. Separate experiments on two distinct TCRs that recognize the MART-1 27–35 (AAGIGILTV) peptide/HLA-A*02 Ag complex characterized single amino acid substitutions in both TCRs that enhanced CD4+ T cell Ag-specific reactivity. These results indicate that simple TCR substitution variants that enhance T cell function can be identified by rapid transfection and assay techniques, providing the means for generating potent Ag complex-specific TCR genes for use in the study of T cell interactions and in T cell adoptive immunotherapy.
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Metadata
- Authors
- Robbins, P. F., Li, Y. F., El-Gamil, M., Zhao, Y., Wargo, J. A., Zheng, Z., Xu, H., Morgan, R. A., Feldman, S. A., Johnson, L. A., Bennett, A. D., Dunn, S. M., Mahon, T. M., Jakobsen, B. K., & Rosenberg, S. A.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05-01
- Volume
- 180
- Issue
- 9
- Pages
- 6116-6131
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1541816872
- Cited by
- 383
- References
- 45
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- green
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- Robbins, P. F., Li, Y. F., El-Gamil, M., Zhao, Y., Wargo, J. A., Zheng, Z., Xu, H., Morgan, R. A., Feldman, S. A., Johnson, L. A., Bennett, A. D., Dunn, S. M., Mahon, T. M., Jakobsen, B. K., & Rosenberg, S. A. (2008). Single and Dual Amino Acid Substitutions in TCR CDRs Can Enhance Antigen-Specific T Cell Functions. The Journal of Immunology. https://doi.org/10.4049/jimmunol.180.9.6116
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