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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.","bibjson":{"author":[{"initials":"J","lastname":"Ekeruche-Makinde","name":"Ekeruche-Makinde J"},{"initials":"JJ","lastname":"Miles","name":"Miles JJ"},{"initials":"HA","lastname":"van den Berg","name":"van den Berg HA"},{"initials":"A","lastname":"Skowera","name":"Skowera A"},{"initials":"DK","lastname":"Cole","name":"Cole DK"},{"initials":"G","lastname":"Dolton","name":"Dolton G"},{"initials":"AJ","lastname":"Schauenburg","name":"Schauenburg AJ"},{"initials":"MP","lastname":"Tan","name":"Tan MP"},{"initials":"JM","lastname":"Pentier","name":"Pentier JM"},{"initials":"S","lastname":"Llewellyn-Lacey","name":"Llewellyn-Lacey S"},{"initials":"KM","lastname":"Miles","name":"Miles KM"},{"initials":"AM","lastname":"Bulek","name":"Bulek AM"},{"initials":"M","lastname":"Clement","name":"Clement M"},{"initials":"T","lastname":"Williams","name":"Williams T"},{"initials":"A","lastname":"Trimby","name":"Trimby A"},{"initials":"M","lastname":"Bailey","name":"Bailey M"},{"initials":"P","lastname":"Rizkallah","name":"Rizkallah P"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"M","lastname":"Peakman","name":"Peakman M"},{"initials":"DA","lastname":"Price","name":"Price DA"},{"initials":"SR","lastname":"Burrows","name":"Burrows SR"},{"initials":"AK","lastname":"Sewell","name":"Sewell AK"},{"initials":"L","lastname":"Wooldridge","name":"Wooldridge L"}],"identifier":[{"id":"10.1182/blood-2012-06-437202","type":"doi"},{"id":"23255554","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Blood","name":""},"pages":[null],"title":"Peptide length determines the outcome of T cell receptor/peptide-MHCI engagement.","type":"article","url":"https://ashpublications.org/blood/article/121/7/1112/31552/Peptide-length-determines-the-outcome-of","volume":[null],"year":[2012]},"in_pmc":"Y","in_pmce":"Y","open_access":"N"},"resolution":"1.77","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/4i4w"},"rcsb":{"url":"https://www.rcsb.org/structure/4i4w"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-A*02:01 binding \"ILAKFLHRL\" at 1.77Å resolution","unique_chain_count":3}}