Studies of tum- peptide analogs define an alternative anchor that can be utilized by Ld ligands lacking the consensus P2 anchor.
To determine how peptides that lack a consensus binding motif interact with class I molecules, we have studied the binding of the tumor-associated tum- P91A 14-22 (tum-) peptide to Ld. Previously, a proline at position 2 (P2) and a hydrophobic residue at P9 had been defined as anchors for Ld ligands. However, the tum- peptide lacks the P2 proline anchor. To compare how peptides with and without the P2 proline anchor bind to Ld, we analyzed the binding of monosubstituted analogues of the murine cytomegalovirus (MCMV) pp89 168-176 and the tum- peptides to Ld. As expected, the binding of both peptides was inhibited by substitutions at P9, the carboxyl-terminal anchor. As also predicted, the MCMV peptide was found to be dependent upon its P2 proline for binding to Ld. By contrast, the binding of the tum- peptide to Ld is dependent primarily on a P8 aspartate residue. Interestingly, the p2Ca peptide that is immunodominant in allorecognition of Ld also lacks the P2 proline anchor and has been shown to depend on residues near the carboxyl terminus for binding to Ld. Furthermore, both the p2Ca and the tum- peptides can bind to Ld as octamers. These combined studies suggest that there are at least two alternative manners by which peptides can bind to Ld. Although most Ld ligands bind using a P2 proline anchor, the tum- and p2Ca peptides bind using alternative anchors in the carboxyl-terminal region.
Robinson
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Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA.
Lee
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DR
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D006649:Histocompatibility Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007739:L Cells; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D006649:Histocompatibility Antigens; D008024:Ligands; D009842:Oligopeptides; D014764:Viral Proteins; C070850:transplantation antigen P91A, mouse