title: A peptide variant of an arthritis-related T cell epitope induces T cells that recognize this epitope as a synthetic peptide but not in its naturally processed form.
abstract: The immune system has the potential to utilize a diverse T cell repertoire for the recognition of Ag in the context of MHC molecules. Here we describe the analysis of two rat T cell clones, both of which recognize a synthetic peptide comprised of the arthritis-associated 180-188 amino acid sequence of the mycobacterial 65-kDa heatshock protein (hsp65 180-188), but which differ in the recognition of the naturally processed hsp65. The arthritogenic T cell clone A2b, generated by immunization with whole Mycobacterium tuberculosis, recognized the hsp65 180-188 synthetic peptide as well as the processed hsp65, whereas T cell clone ATL11, generated after immunization with a single amino acid substituted peptide analog of hsp65 180-188, recognized peptide hsp65 180-188 but not the processed hsp65. For both T cell clones the minimal stimulatory sequence was hsp65 180-186. However, within this minimal stimulatory sequence marked differences between the clones were found with regard to peptide residues interacting with the TCR. Furthermore, addition of extra residues at the N terminus of the hsp65 180-186 sequence abrogated the recognition by clone ATL11, but not by A2b. These findings demonstrate that, upon in vivo immunization with a synthetic peptide comprised of a single amino acid variant of a T cell epitope, T cells can be triggered that recognize a peptide comprised of the original epitope sequence, but that do not recognize this epitope in its naturally processed protein fragment. The possibility of triggering such T cells by immunization with synthetic peptides, may well have consequences for the design of peptide vaccines or peptide immunomodulatory agents.
authors.affiliation: Department of Immunology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Wauben
authors.forename: R
authors.initials: R
authors.lastname: van der Zee
authors.forename: I
authors.initials: I
authors.lastname: Joosten
authors.forename: C J
authors.initials: CJ
authors.lastname: Boog
authors.forename: A M
authors.initials: AM
authors.lastname: van Dijk
authors.forename: M C
authors.initials: MC
authors.lastname: Holewijn
authors.forename: R H
authors.initials: RH
authors.lastname: Meloen
authors.forename: W
authors.initials: W
authors.lastname: van Eden
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001665:Binding Sites; D000939:Epitopes / Q000032:analysis*; D006360:Heat-Shock Proteins / Q000032:analysis / Q000276:immunology*; D007114:Immunization; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000939:Epitopes; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell