5T6Y

HLA-B*57:01 presenting TSTFEDVKILAF

Summary for 5T6Y

• Entry DOI: 10.2210/pdb5t6y/pdb
• Related: 5T6W 5T6X 5T6Z 5T70
• Descriptor: HLA class I histocompatibility antigen, B-57 alpha chain, Beta-2-microglobulin, Decapeptide: THR-SER-THR-PHE-GLU-ASP-VAL-LYS-ILE-LEU-ALA-PHE, ... (6 entities in total)
• Functional Keywords: human leukocyte antigen immunoglobulin domain antigen presentation, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P18465; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 3
• Total formula weight: 45191.21

Authors

Pymm, P.,Rossjohn, J.,Vivian, J.P. (deposition date: 2016-09-02, release date: 2017-03-01, Last modification date: 2023-10-04)

Primary citation

Pymm, P.,Illing, P.T.,Ramarathinam, S.H.,O'Connor, G.M.,Hughes, V.A.,Hitchen, C.,Price, D.A.,Ho, B.K.,McVicar, D.W.,Brooks, A.G.,Purcell, A.W.,Rossjohn, J.,Vivian, J.P.
MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape.
Nat. Struct. Mol. Biol., 24:387-394, 2017

PubMed Abstract: Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove. The common escape mutant TSNLQEQIGW bound HLA-B*57:01 canonically, adopting a dramatically different conformation than the TW10 peptide. This affected recognition by killer cell immunoglobulin-like receptor (KIR) 3DL1 expressed on NK cells. We thus define a previously uncharacterized feature of the human leukocyte antigen class I (HLA-I) immunopeptidome that has implications for viral immune escape. We further suggest that recognition of the HLA-B*57:01-TW10 epitope is governed by a 'molecular tension' between the adaptive and innate immune systems.

PubMed: 28218747
DOI: 10.1038/nsmb.3381

Experimental method

X-RAY DIFFRACTION (1.76 Å)