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However, this lipid-modifying reaction creates a novel class of \"lipopeptide\" Ags targeted by host CTLs. The primate MHC class I-encoded protein, Mamu-B*098, was previously shown to bind <i>N</i>-myristoylated 5-mer peptides. Nevertheless, T cells exist that recognize even shorter lipopeptides, and much remains to be elucidated concerning the molecular mechanisms of lipopeptide presentation. We, in this study, demonstrate that the MHC class I allele, Mamu-B*05104, binds the <i>N</i>-myristoylated 4-mer peptide (C14-Gly-Gly-Ala-Ile) derived from the viral Nef protein for its presentation to CTLs. A phylogenetic tree analysis indicates that these classical MHC class I alleles are not closely associated; however, the high-resolution x-ray crystallographic analyses indicate that both molecules share lipid-binding structures defined by the exceptionally large, hydrophobic B pocket to accommodate the acylated glycine (G1) as an anchor. The C-terminal isoleucine (I4) of C14-Gly-Gly-Ala-Ile anchors at the F pocket, which is distinct from that of Mamu-B*098 and is virtually identical to that of the peptide-presenting MHC class I molecule, HLA-B51. The two central amino acid residues (G2 and A3) are only exposed externally for recognition by T cells, and the methyl side chain on A3 constitutes a major T cell epitope, underscoring that the epitopic diversity is highly limited for lipopeptides as compared with that for MHC class I-presented long peptides. These structural features suggest that lipopeptide-presenting MHC class I alleles comprise a distinct MHC class I subset that mediates an alternative pathway for CTL activation.","bibjson":{"author":[{"initials":"Y","lastname":"Yamamoto","name":"Yamamoto Y"},{"initials":"D","lastname":"Morita","name":"Morita D"},{"initials":"Y","lastname":"Shima","name":"Shima Y"},{"initials":"A","lastname":"Midorikawa","name":"Midorikawa A"},{"initials":"T","lastname":"Mizutani","name":"Mizutani T"},{"initials":"J","lastname":"Suzuki","name":"Suzuki J"},{"initials":"N","lastname":"Mori","name":"Mori N"},{"initials":"T","lastname":"Shiina","name":"Shiina T"},{"initials":"H","lastname":"Inoko","name":"Inoko H"},{"initials":"Y","lastname":"Tanaka","name":"Tanaka Y"},{"initials":"B","lastname":"Mikami","name":"Mikami B"},{"initials":"M","lastname":"Sugita","name":"Sugita M"}],"identifier":[{"id":"10.4049/jimmunol.1900087","type":"doi"},{"id":"31043477","type":"pubmed"}],"issue":["12"],"journal":{"iso_abbreviation":"J. Immunol.","name":""},"pages":["3349-3358"],"title":"Identification and Structure of an MHC Class I-Encoded Protein with the Potential to Present <i>N</i>-Myristoylated 4-mer Peptides to T Cells.","type":"article","url":"http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.1900087","volume":["202"],"year":[2019]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"1.80","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6iwg"},"rcsb":{"url":"https://www.rcsb.org/structure/6iwg"}},"species":{"common_name":"rhesus monkey","match_type":"histo:assign_species","scientific_name":"Macaca mulatta","slug":"macaca_mulatta"},"tcr":null,"title":"Mamu-B*051:04 possibly without \"peptide\" at 1.80&#8491; resolution","unique_chain_count":2}}
