title: Peptide dependency of alloreactive CD4+ T cell responses.
abstract: Alloreactivity, the capacity of a large number of T lymphocytes to react with foreign MHC molecules, represents the cellular basis for the rejection of tissue grafts. Although it was originally assumed that the TCR of alloreactive T cells focus their recognition on the polymorphic residues that differ between the MHC molecules of responder and stimulator cells, studies in the MHC class I system have clearly demonstrated that MHC-bound peptides can influence this interaction. It remains unclear, however, whether peptides play an equally important role for the recognition of MHC class II molecules by alloreactive CD4+ T cells. Another issue that remains unresolved is the overall frequency of peptide-dependent versus peptide-independent alloreactive T cells. We have addressed these questions with antigen-presenting cells (APC) from H2-M mutant mice that predominantly express a single MHC class II-peptide complex, H2-Ab bound by a peptide (CLIP) derived from the class II-associated invariant chain. APC from these mice were used as targets and stimulators for alloreactive CD4+ T cells. Results demonstrated that the vast majority of CD4+ alloreactive T cells recognize MHC class II molecules in a peptide-dependent fashion.
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Mendiratta
authors.forename: J P
authors.initials: JP
authors.lastname: Kovalik
authors.forename: S
authors.initials: S
authors.lastname: Hong
authors.forename: N
authors.initials: N
authors.lastname: Singh
authors.forename: W D
authors.initials: WD
authors.lastname: Martin
authors.forename: L
authors.initials: L
authors.lastname: Van Kaer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D006183:H-2 Antigens; C108513:H-2A antigen; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides; C045084:invariant chain