title: Self tolerance to T cell receptor V beta sequences.
abstract: T cell tolerance to self is achieved by deletion or inactivation of clones recognizing peptides of self proteins presented by major histocompatibility complex molecules. A considerable fraction of self proteins accessible to the immune system is contributed by the system itself, for example, the receptors used for antigen recognition (antibodies and T cell receptors [TCRs]). Thus far, it has remained unclear, whether antigen receptors are subject to self tolerance, or on contrary, engage into network interactions implying immunity rather than tolerance. In this study, we demonstrate self tolerance to synthetic peptides corresponding to the first hypervariable region of the V beta 8.1 and V beta 8.2 TCR proteins. We also show that the tolerogenic synthetic peptide corresponds to a fragment produced by processing of the V beta protein, and conversely, that a V beta peptide not produced by processing is also not subject to self tolerance. Thus, the rules of tolerance seem to apply to antigen receptors, at least to their germline-encoded portions, in a similar fashion as to other self proteins. This finding has important implications for studies of natural and artificially induced immune networks.
authors.affiliation: Department of Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA.
authors.forename: F
authors.initials: F
authors.lastname: Falcioni
authors.forename: D
authors.initials: D
authors.lastname: Vidović
authors.forename: E S
authors.initials: ES
authors.lastname: Ward
authors.forename: D
authors.initials: D
authors.lastname: Bolin
authors.forename: G
authors.initials: G
authors.lastname: Singh
authors.forename: H
authors.initials: H
authors.lastname: Shah
authors.forename: B
authors.initials: B
authors.lastname: Ober
authors.forename: Z A
authors.initials: ZA
authors.lastname: Nagy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D003433:Crosses, Genetic; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006183:H-2 Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta