title: A basis for alloreactivity: MHC helical residues broaden peptide recognition by the TCR.
abstract: The high frequency of alloreactive T cells is a major hindrance for transplantation; however, the molecular basis for alloreactivity remains elusive. We examined the I-Ep alloreactivity of a well-characterized Hb(64-76)/I-Ek-specific murine T cell. Using a combinatorial peptide library approach, we identified a highly stimulatory alloepitope mimic and observed that the recognition of the central TCR contact residues (P3 and P5) was much more flexible than that seen with Hb(64-76)/I-Ek, but still specific. Therefore, alloreactive T cells can recognize a self-peptide/MHC surface; however, the allogeneic MHC molecule changes the recognition requirements for the central region of the peptide, allowing a more diverse repertoire of ligands to be recognized.
authors.affiliation: Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: C
authors.initials: C
authors.lastname: Daniel
authors.forename: S
authors.initials: S
authors.lastname: Horvath
authors.forename: P M
authors.initials: PM
authors.lastname: Allen
mesh_terms: D000818:Animals; D016466:CHO Cells; D022801:Complementarity Determining Regions; D006224:Cricetinae; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas; D007137:Immunoglobulin alpha-Chains / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010449:Peptide Mapping; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D022801:Complementarity Determining Regions; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007137:Immunoglobulin alpha-Chains; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell