title: On Peptides and Altered Peptide Ligands: From Origin, Mode of Action and Design to Clinical Application (Immunotherapy).
abstract: T lymphocytes equipped with clonotypic T cell antigen receptors (TCR) recognize immunogenic peptides only when presented in the context of their own major histocompatibility complex (MHC) molecules. Peptide loading to MHC molecules occurs in intracellular compartments (ER for class I and MIIC for class II molecules) and relies on the interaction of the respective peptides and peptide binding pockets on MHC molecules. Those peptide residues not engaged in MHC binding point towards the TCR screening for possible peptide MHC complex binding partners. Natural or intentional modification of both MHC binding registers and TCR interacting residues of peptides - leading to the formation of altered peptide ligands (APLs) - might alter the way peptides interact with TCRs and hence influence subsequent T cell activation events, and consequently T cell effector functions. This review article summarizes how APLs were detected and first described, current concepts of how APLs modify T cellular signaling, which biological mechanisms might force the generation of APLs in vivo, and how peptides and APLs might be used for the benefit of patients suffering from allergic or autoimmune diseases.
authors.affiliation: Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Martín
authors.initials: M
authors.lastname: Candia
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kratzer
authors.forename: Winfried F
authors.initials: WF
authors.lastname: Pickl
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation; D002454:Cell Differentiation; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D000939:Epitopes / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000939:Epitopes; D006649:Histocompatibility Antigens; D016056:Immunodominant Epitopes; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell