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Ekeruche-Makinde, Julia; Miles, John J.; van den Berg, Hugo A.; Skowera, Ania; Cole, David K.; Dolton, Garry; Schauenburg, Andrea J.A.; Tan, Mai Ping; Pentier, Johanne M.; Llewellyn-Lacey, Sian; Miles, Kim M.; Bulek, Anna M.; Clement, Mathew; Williams, Tamsin; Trimby, Andrew; Bailey, Mick; Rizkallah, Pierre; Rossjohn, Jamie; Peakman, Mark; Price, David A.; Burrows, Scott R.; Sewell, Andrew K.; Wooldridge, Linda
Blood, 02/2013, Letnik: 121, Številka: 7Journal Article
αβ-TCRs expressed at the CD8+ T-cell surface interact with short peptide fragments (p) bound to MHC class I molecules (pMHCI). The TCR/pMHCI interaction is pivotal in all aspects of CD8+ T-cell immunity. However, the rules that govern the outcome of TCR/pMHCI engagement are not entirely understood, and this is a major barrier to understanding the requirements for both effective immunity and vaccination. In the present study, we discovered an unexpected feature of the TCR/pMHCI interaction by showing that any given TCR exhibits an explicit preference for a single MHCI-peptide length. Agonists of nonpreferred length were extremely rare, suboptimal, and often entirely distinct in sequence. Structural analysis indicated that alterations in peptide length have a major impact on antigenic complexity, to which individual TCRs are unable to adapt. This novel finding demonstrates that the outcome of TCR/pMHCI engagement is determined by peptide length in addition to the sequence identity of the MHCI-bound peptide. Accordingly, the effective recognition of pMHCI Ag, which is a prerequisite for successful CD8+ T-cell immunity and protective vaccination, can only be achieved by length-matched Ag-specific CD8+ T-cell clonotypes. •MHCI-restricted TCRs exhibit an explicit preference for a single MHCI-peptide length.•Effective CD8+ T-cell immunity can only be achieved by length-matched Ag-specific T-cell clonotypes.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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