T cell-mediated immunity is thought to play an important role in the pathogenesis of WG. In previous studies a minority of WG patients as well as some healthy controls showed in vitro proliferation of their peripheral blood mononuclear cells (PBMC) to PR3, the main
autoantigen in WG. The relevant
peptides responsible for this in vitro proliferation have not been identified. In order to define immunogenic
peptides, PBMC of 13 WG patients in remission and 10 healthy controls were tested for proliferation to linear
peptides of PR3 and to whole PR3. Fifty overlapping
peptides spanning the whole PR3 sequence were synthesized.
Peptides were tested in pools of five
peptides and as single
peptide. PBMC of two WG patients and one healthy control proliferated to whole PR3 and to
peptide pools. In addition, 10 WG patients and eight healthy controls that did not proliferate to whole PR3 did proliferate to pools of PR3
peptides. Although more WG patients tended to react to particular
peptide pools, no significant difference was seen between lymphocyte proliferation to PR3
peptides of WG patients and that of healthy controls. The pools of
peptides recognized were mainly located at the N- and C-terminus of PR3. No correlation was observed between HLA type and proliferation on particular
peptide pools. No proliferation of PBMC was observed to single
peptides. In conclusion, T cells of WG patients proliferate in vitro more frequently to PR3
peptides than to the whole PR3
protein.
Peptides derived from the
signal sequence, the propeptide or
peptides located at the C-terminus of PR3 induce highest levels of proliferation. No specific PR3 sequence could be identified that was preferentially recognized by PBMC of WG patients compared with controls.