Major histocompatibility complex conformational epitopes are peptide specific.
Serologically distinct forms of H-2Kb are stabilized by loading cells expressing "empty" class I major histocompatibility complex (MHC) molecules with different H-2Kb binding peptides. The H-2Kb epitope recognized by monoclonal antibody (mAb) 28.8.6 was stabilized by ovalbumin (OVA) (257-264) and murine cytomegalovirus (MCMV) pp89 (168-176) peptides, but not by vesicular stomatic virus nucleoprotein (VSV NP) (52-59) and influenza NP (Y345-360) peptides. The H-2Kb epitope recognized by mAb 34.4.20 was stabilized by VSV NP (52-59) peptide but not by OVA (257-264), MCMV pp89 (168-176), or influenza NP (Y345-360) peptides. Immunoprecipitation of H-2Kb molecules from normal cells showed that 28.8.6 and 34.4.20 epitopes were only present on a subset of all conformationally reactive H-2Kb molecules. Using alanine-substituted derivatives of the VSV peptide, the 28.8.6 epitope was completely stabilized by substitution of the first residue and partially stabilized by substitution of the third or the fifth residues in the peptides. These results indicate that distinct conformational MHC epitopes are dependent on the specific peptide that occupies the antigenic peptide binding groove on individual MHC molecules. The changes in MHC epitopes observed may also be important in understanding the diversity of T cell receptors used in an immune response and the influence of peptides on development of the T cell repertoire.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D007739:L Cells; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011487:Protein Conformation; D014162:Transfection; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006183:H-2 Antigens; D010455:Peptides; D014764:Viral Proteins; D010047:Ovalbumin