title: Modification of human T-cell responses by altered peptide ligands: a new approach to antigen-specific modification.
abstract: Human CD4+ T-cells recognize antigenic peptides in the context of human leukocyte antigen (HLA) class II molecules and produce various lymphokines to proliferate and activate other cells. It was once considered that the T-cell response is an all or nothing type event, but recent studies have clearly indicated that T-cells show many different types of activation in recognition of altered ligands for T-cell receptors (TCR). In this review, we summarize our recent findings on the human CD4+ T-cell response to altered peptide ligands (APL); peptides carrying single residue substitutions in antigenic peptides. We observed the following: 1) TCR antagonism for T-cell clones reactive to non-self or autoantigenic peptides, 2) partial activation (agonism) without cell proliferation, including production of lymphokines and increases in cell size, and in expression levels of several cell surface proteins or survival time in the absence of antigenic stimulus, 3) augmentation in cell proliferation and production of interferon-gamma (IFN-gamma) and granulocyte monocyte colony stimulating factor (GM-CSF), 4) augmentation of interleukin (IL)-12 production by antigen presenting cell (APC) and the subsequent augmented production of IFN-gamma by T-cells. This information provides basic knowledge regarding the characteristics of T-cell recognition of antigens and the subsequent activation, and a novel method for modification of human T-cell responses by altered peptide ligands (APLs), as a possible candidate for antigen-specific immunopotentiating or immunosuppressive therapy against autoimmune diseases, allergies, infectious diseases and malignant tumors.
authors.affiliation: Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences.
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Kanai
authors.forename: H
authors.initials: H
authors.lastname: Yokomizo
authors.forename: T
authors.initials: T
authors.lastname: Matsuoka
authors.forename: S
authors.initials: S
authors.lastname: Matsushita
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D008024:Ligands; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008925:Mites / Q000276:immunology; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D051020:bcl-X Protein
chemical_list: D000941:Antigens; D000942:Antigens, Bacterial; D001324:Autoantigens; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D006681:HLA-D Antigens; D008024:Ligands; D008222:Lymphokines; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D011950:Receptors, Cholinergic; D051020:bcl-X Protein; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)