title: A mAb against HLA-A2 can be influenced both positively and negatively by the associated peptide.
abstract: Presentation of peptides by class I HLA molecules is essential for the development of a T cell-mediated immune response. TCRs have the ability to discriminate among large numbers of different HLA-peptide complexes. We have identified a mAb, MA2.1, that also discriminates among HLA-A2 associated with different peptides. A soluble form of HLA-A2 bound to single peptides was prepared and its serological reactivity was studied using four mAbs. Three antibodies, W6/32, BB7.2 and BBM.1, recognized all the complexes equally. MA2.1, however, recognized most of the complexes equally but showed markedly different reactivity to two peptides bound to HLA-A2. MA2.1 recognized HLA-A2 complexed with the HIV-1 p17 epitope (SLYNTVATL) at least 30 times more strongly than all other complexes studied and this enhanced reactivity was found to be sensitive to a point mutation of threonine to alanine at position 8 in the peptide. In addition, MA2.1 had a very low reactivity for HLA-A2 complexed with the peptide TLWVDPYEV. Previous studies have mapped the binding epitope of MA2.1 to the alpha 1 and alpha 2 helices of HLA-A2, suggesting two possible explanations for the ability of the bound peptide to influence MA2.1 reactivity. Either MA2.1 is sensitive to peptide-induced conformational changes of the helices, or it directly contacts certain peptides in the groove of HLA-A2.
authors.affiliation: Nuffield Department of Clinical Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Barouch
authors.forename: M
authors.initials: M
authors.lastname: Davenport
authors.forename: A
authors.initials: A
authors.lastname: McMichael
authors.forename: P
authors.initials: P
authors.lastname: Reay
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D017951:Antigen Presentation; D003546:Cysteine Endopeptidases; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D017354:Point Mutation; D011506:Proteins / Q000276:immunology; D012194:RNA-Directed DNA Polymerase / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D015683:Gene Products, gag; D015488:HIV Antigens; D015789:HLA-A2 Antigen; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011506:Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; C071313:LMP-2 protein; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D003546:Cysteine Endopeptidases