کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5917734 | 1163798 | 2011 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Real time detection of peptide-MHC dissociation reveals that improvement of primary MHC-binding residues can have a minimal, or no, effect on stability
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کلمات کلیدی
FACSMFITCrpMHCSPR - تشدید پلاسمون سطحیSurface plasmon resonance - تشدید پلاسمون سطحیfluorescent activated cell sorting - دسته بندی سلول فعال فلورسنت فعال استSurface plasmon resonance (SPR) - رزونانس پلاسما سطح (SPR)T-cells - سلولهای Tmean fluorescence intensity - میانگین شدت فلورسانسCancer vaccines - واکسن های سرطانیT-cell receptor - گیرنده لنفوسیت T
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
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چکیده انگلیسی
The majority of known major histocompatibility complex class I (MHCI)-associated tumor-derived peptide antigens do not contain an optimal motif for MHCI binding. As a result, anchor residue-modified 'heteroclitic' peptides have been widely used in therapeutic cancer vaccination trials in order to enhance immune responsiveness. In general, the improved stability of these heteroclitic complexes has been inferred from their improved immunogenicity but has not been formally assessed. Here, we investigated the binding of 4 HLA A*0201-restricted tumor-derived peptides and their commonly used heteroclitic variants. We utilized a cell surface binding assay and a novel robust method for testing the durability of soluble recombinant pMHCI in real time by surface plasmon resonance. Surprisingly, we show that heteroclitic peptides designed with optimal MHC binding motifs do not always form pMHCs that are substantially more stable than their wildtype progenitors. These findings, combined with our recent discovery that TCRs can distinguish between wildtype peptides and those altered at a primary buried MHC anchor residue, suggest that altered TCR binding may account for a large part of the increased immune response that can be generated by anchor residue-modified ligands. Our results further highlight the fact that heteroclitic peptide-based immune interventions require careful evaluation to ensure that wildtype antigen specificity is maintained in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 48, Issue 4, January 2011, Pages 728-732
Journal: Molecular Immunology - Volume 48, Issue 4, January 2011, Pages 728-732
نویسندگان
Kim M. Miles, John J. Miles, Florian Madura, Andrew K. Sewell, David K. Cole,