Altered peptide ligand design: altering immune responses to class I MHC/peptide complexes.
Class I proteins are responsible for binding proteins from endogenously synthesized proteins and displaying them on the cell surface. Our understanding of this process has reached the point where we can manipulate the biochemical properties of peptide/class I binding and determine the effects of this alteration on subsequent immune responses. In this article, we will review the biochemistry of peptide/class I binding, and the effects of structure on this interaction between class I proteins and their peptide ligands. We will review the data which suggest that the major relevant biochemical parameter of class I peptide binding is the off-rate. We will show that the design of altered ligands with improved binding, thermostability and immunogenicity is possible.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, USA. collins1@med.unc.edu
E J
EJ
Collins
J A
JA
Frelinger
D017951:Antigen Presentation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D009154:Mutation; D010455:Peptides / Q000737:chemistry* / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D007143:Immunoglobulin Heavy Chains; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell