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
Mhm. Wauben et al., 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 Journal of immunology, 150(12), 1993, pp. 5722-5730
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.