Peptide ligand structure influences the exchange of beta2-microglobulin by cell surface Kb.
We have studied the interactions which occur between the peptide ligand and beta2-microglobulin (beta2m) components of the class I MHC complex by analysing the process of beta2m exchange. We have previously shown that the rate of beta2m exchange on a cell-surface class I MHC complex varies with the peptide ligand to which it is bound. It remains unclear, however, whether the ability of peptide ligand to alter beta2m/heavy-chain association is related to peptide affinity, peptide structure, or both. In this article, we examine the effects of variations in peptide ligand structure on the rate of beta2m exchange by cell surface Kb complexes. Using a panel of alanine substituted variants of the MCMV peptide (YPHFMPTNL), we show that single amino acid changes in peptide sequence can have dramatic effects on the rates of beta2m exchange. The observed changes in beta2m exchange rates are directly due to modification of the peptide ligand structure as they do not reflect changes in peptide affinity. These findings suggest that peptide ligand structure can induce conformational changes in the Kb heavy chain which alter the rates of cell surface beta2m exchange, and provide further evidence for peptide-dependent fluidity of the class I heavy chain.
Cook
J R
JR
Washington University School of Medicine, Department of Genetics, St Louis, MO 63110, USA.
Myers
N B
NB
Hansen
T H
TH
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000032:analysis; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D018146:Muromegalovirus / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation; D001613:beta 2-Microglobulin / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007143:Immunoglobulin Heavy Chains; D007457:Iodine Radioisotopes; D008024:Ligands; D008565:Membrane Proteins; D010455:Peptides; D001613:beta 2-Microglobulin; D000409:Alanine