title: Major histocompatibility complex class I molecules bind natural peptide ligands lacking the amino-terminal binding residue in vivo.
abstract: Major histocompatibility complex (MHC) class I-peptide complexes are stabilized by multiple interactions, including those of the peptidic NH(2)-terminal group in the A pocket of the MHC molecule. In this study, the characterization of four natural HLA-B39 ligands lacking the amino-terminal binding residue is reported. These peptides were found in the endogenous peptide pool of one or more of the B*3901, B*3905, and B*3909 allotypes and sequenced by nanoelectrospray mass spectrometry. Control experiments ruled out that they resulted from exopeptidase trimming of their NH(2)-terminally extended counterparts: NAc-SHVAVENAL, EHGPNPIL, IHEPEPHIL, and EHAGVISVL, also present in the same peptide pools, during purification. HAGVISVL and HVAVENAL behaved similarly to the corresponding NH(2)-terminally extended peptides in their binding to B*3901 and B*3909 at the cell surface in vitro, and in cell surface stabilization of B*3901. This is, to our knowledge, the first demonstration that peptides lacking the amino-terminal binding residue bind in vivo to classical MHC class I molecules. The results indicate that canonical MHC-peptide interactions in the A pocket are not always necessary for endogenous peptide presentation.
authors.affiliation: Centro de Biologia Molecular Severo Ochoa (Consejo Superior de Investigaciones Cientificas), Universidad Autónoma de Madrid, Facultad de Ciencias, 28049 Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Yague
authors.forename: A
authors.initials: A
authors.lastname: Marina
authors.forename: J
authors.initials: J
authors.lastname: Vazquez
authors.forename: J A
authors.initials: JA
authors.lastname: Lopez De Castro
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D015235:HLA-B Antigens / Q000378:metabolism*; D059946:HLA-B39 Antigen; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015235:HLA-B Antigens; D059946:HLA-B39 Antigen; D008024:Ligands; D010455:Peptides