4I4W

Peptide length determines the outcome of T cell receptor/peptide-MHCI engagement

Summary for 4I4W

• Entry DOI: 10.2210/pdb4i4w/pdb
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Immunogenic peptide, ... (7 entities in total)
• Functional Keywords: mhc i fold, antigen presentation, t-cell receptor, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted : P61769
• Total number of polymer chains: 3
• Total formula weight: 46529.72

Authors

Rizkallah, P.J.,Wooldridge, L.,Cole, D.K. (deposition date: 2012-11-28, release date: 2013-01-02, Last modification date: 2024-11-06)

Primary citation

Ekeruche-Makinde, J.,Miles, J.J.,van den Berg, H.A.,Skowera, A.,Cole, D.K.,Dolton, G.,Schauenburg, A.J.,Tan, M.P.,Pentier, J.M.,Llewellyn-Lacey, S.,Miles, K.M.,Bulek, A.M.,Clement, M.,Williams, T.,Trimby, A.,Bailey, M.,Rizkallah, P.J.,Rossjohn, J.,Peakman, M.,Price, D.A.,Burrows, S.R.,Sewell, A.K.,Wooldridge, L.
Peptide length determines the outcome of TCR/peptide-MHCI engagement.
Blood, 121:1112-1123, 2013

PubMed Abstract: 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.

PubMed: 23255554
DOI: 10.1182/blood-2012-06-437202

Experimental method

X-RAY DIFFRACTION (1.77 Å)