title: Anti-coreceptor antibodies profoundly affect staining with peptide-MHC class I and class II tetramers.
abstract: The T cell coreceptors CD8 and CD4 bind to invariable regions of peptide-MHC class I (pMHCI) and class II (pMHCII) molecules, respectively, and facilitate antigen recognition by a number of mechanisms. It is established that some antibodies (Ab) specific for the CD8 molecule, which stabilizes TCR/pMHCI interactions, can alter the binding of pMHCI tetramers to cell surface TCR. In contrast, the extremely weak pMHCII/CD4 interaction does not stabilize TCR/pMHCII interactions or contribute to cognate tetramer binding; consequently, it is assumed that anti-CD4 Ab do not affect pMHCII binding. Here, we used a panel of point-mutated HLA A2 molecules with a range of affinities for CD8 spanning over three orders of magnitude to demonstrate that anti-CD8 Ab-mediated inhibition of pMHCI tetramer binding and cognate T cell activation correlates directly with the strength of the pMHCI/CD8 interaction. Further, some anti-CD4 Ab were found to block pMHCII tetramer binding; these effects were also paralleled in T cell activation assays. In sum, these data challenge the assertion that anti-coreceptor Ab exert their effects on T cell activation and pMHC binding solely by blocking pMHC/coreceptor interactions.
authors.affiliation: T-cell Modulation Group, The Peter Medawar Building for Pathogen Research, Oxford, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Wooldridge
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Anita
authors.initials: A
authors.lastname: Milicic
authors.forename: Bruno
authors.initials: B
authors.lastname: Laugel
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sewell
mesh_terms: D000595:Amino Acid Sequence; D019138:Antibodies, Blocking / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D013194:Staining and Labeling
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents