title: Modulation of peptide-dependent allospecific epitopes on HLA-DR4 molecules by HLA-DM.
abstract: Peptide binding to HLA-DR molecules in intracellular compartments is facilitated by HLA-DM molecules, present in most types of antigen-presenting cells. Allorecognition of DR specificities represents a form of T cell recognition of the MHC-peptide complex which in some cases is influenced by peptide binding. DRA and DRB*0401 (Dw4) genes were introduced into different cell types including DM-negative and DM-restored mutant cells to analyze recognition of DR4 subtypes by alloreactive T cell clones and Dw4-specific monoclonal antibodies. Distinct patterns of T cell recognition were identified: (i) deficient response to Dw4 molecules in the absence of DM expression in which T cell responses were restored by transfecting DM into the Dw4-expressing cells; and (ii) equivalent recognition of Dw4 on DM- and DM+ cells. Using several mAb to Dw4 molecules, a similar distinction was observed: a shared epitope on Dw4 and Dw14 molecules was partially DM-independent while a Dw4-specific epitope was DM-dependent and cell type-specific. Thus, a subset of both T cell and mAb allodeterminants are influenced by a DM-dependent interaction of MHC molecules with peptides, while the formation of DM-independent allodeterminants may represent direct MHC epitope recognition by the T cell receptor or an alternative peptide loading mechanism distinct from the HLA-DM pathways.
authors.affiliation: Immunology and Diabetes Programs, Virginia Mason Research Center, Seattle, WA 98101, USA.
authors.forename: S
authors.initials: S
authors.lastname: Drover
authors.forename: S
authors.initials: S
authors.lastname: Kovats
authors.forename: S
authors.initials: S
authors.lastname: Masewicz
authors.forename: J S
authors.initials: JS
authors.lastname: Blum
authors.forename: G T
authors.initials: GT
authors.lastname: Nepom
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002461:Cell Line, Transformed; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology*; D015804:HLA-DR4 Antigen / Q000276:immunology*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D010455:Peptides