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

The immune system has the potential to utilize a diverse T cell repert oire for the recognition of Ag in the context of MHC molecules. Here w e describe the analysis of two rat T cell clones, both of which recogn ize a synthetic peptide comprised of the arthritis-associated 180-188 amino acid sequence of the mycobacterial 65-kDa heatshock protein (hsp 65 180-188), but which differ in the recognition of the naturally proc essed hsp65. The arthritogenic T cell clone A2b, generated by immuniza tion with whole Mycobacterium tuberculosis, recognized the hsp65 180-1 88 synthetic peptide as well as the processed hsp65, whereas T cell cl one ATL11, generated after immunization with a single amino acid subst ituted peptide analog of hsp65 180-188, recognized peptide hsp65 180-1 88 but not the processed hsp65. For both T cell clones the minimal sti mulatory sequence was hsp65 180-186. However, within this minimal stim ulatory sequence marked differences between the clones were found with regard to peptide residues interacting with the TCR. Furthermore, add ition of extra residues at the N terminus of the hsp65 180-186 sequenc e abrogated the recognition by clone ATL11, but not by A2b. These find ings demonstrate that, upon in vivo immunization with a synthetic pept ide comprised of a single amino acid variant of a T cell epitope, T ce lls can be triggered that recognize a peptide comprised of the origina l epitope sequence, but that do not recognize this epitope in its natu rally processed protein fragment. The possibility of triggering such T cells by immunization with synthetic peptides, may well have conseque nces for the design of peptide vaccines or peptide immunomodulatory ag ents.