title: Identities of P2 and P3 Residues of H-2Kb-Bound Peptides Determine Mouse Ly49C Recognition.
abstract: Ly49 receptors can be peptide selective in their recognition of MHC-I-peptide complexes, affording them a level of discrimination beyond detecting the presence or absence of specific MHC-I allele products. Despite this ability, little is understood regarding the properties that enable some peptides, when bound to MHC-I molecules, to support Ly49 recognition, but not others. Using RMA-S target cells expressing MHC-I molecules loaded with individual peptides and effector cells expressing the ectodomain of the inhibitory Ly49C receptor, we found that two adjacent amino acid residues, P2 and P3, both buried in the peptide binding groove of H-2Kb, determine mouse Ly49C specificity. If both are aliphatic residues, this is supportive. Whereas, small amino acids at P2 and aromatic amino acids at the P3 auxiliary anchor residue are detrimental to Ly49C recognition. These results resemble those with a rat Ly49 where the identity of a peptide anchor residue determines recognition, suggesting that dependence on specific peptide residues buried in the MHC-I peptide-binding groove may be fundamental to Ly49 peptide selectivity and recognition.
authors.affiliation: Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Elsa A
authors.initials: EA
authors.lastname: Marquez
authors.affiliation: Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Kane
mesh_terms: D000483:Alleles; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D006183:H-2 Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D051381:Rats; D055630:Receptors, NK Cell Lectin-Like / Q000378:metabolism
chemical_list: D000596:Amino Acids; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; C408902:MHC binding peptide; D055650:NK Cell Lectin-Like Receptor Subfamily A; D009842:Oligopeptides; D010455:Peptides; D055630:Receptors, NK Cell Lectin-Like