Journal
JOURNAL OF IMMUNOLOGY
Volume 185, Issue 4, Pages 2600-2610Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1000629
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Funding
- Biotechnology and Biological Sciences Research Council [BB/H001085/1]
- Wellcome Trust
- Department of Health via the National Institute for Health Research Comprehensive Biomedical Research Center
- St. Thomas' National Health Service Foundation Trust
- King's College London
- Juvenile Diabetes Research Foundation [7-2005-877]
- BBSRC [BB/H001085/1] Funding Source: UKRI
- MRC [G0501963] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/H001085/1] Funding Source: researchfish
- Medical Research Council [G0501963] Funding Source: researchfish
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Improving T cell Ags by altering MHC anchor residues is a common strategy used to enhance peptide vaccines, but there has been little assessment of how such modifications affect TCR binding and T cell recognition. In this study, we use surface plasmon resonance and peptide-MHC tetramer binding at the cell surface to demonstrate that changes in primary peptide anchor residues can substantially and unpredictably alter TCR binding. We also demonstrate that the ability of TCRs to differentiate between natural and anchor-modified heteroclitic peptides distinguishes T cells that exhibit a strong preference for either type of Ag. Furthermore, we show that anchor-modified heteroclitic peptides prime T cells with different TCRs compared with those primed with natural Ag. Thus, vaccination with heteroclitic peptides may elicit T cells that exhibit suboptimal recognition of the intended natural Ag and, consequently, impaired functional attributes in vivo. Heteroclitic peptide-based immune interventions therefore require careful evaluation to ensure efficacy in the clinic. The Journal of Immunology, 2010, 185: 2600-2610.
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