Several proteins are investigated as candidate auto-antigens in the pathogenesis of Behçet's disease (BD). This study aimed to screen the cellular responses to auto-antigen (alphaB-crystallin, alphaBC), and microorganism (Streptococcus sangius KTH-1 BES-1 protein) derived peptides as well as to isopentenyl pyrophosphate (IPP). Peripheral blood mononuclear cells (PBMC) from 22 BD patients and 22 healthy controls (HC) were stimulated in vitro with alphaBC, BES-1 peptides, IPP and PPD and induced proliferation as well as the secreted interleukin (IL)-12 and interferon (IFN)-gamma production levels were measured. We did not observe any significant difference in cellular proliferation between BD patients and HC. Induction of IL-12 secretion with alphaBC was stronger in BD patients (P = 0.04) and in the disease subgroup with uveitis (P = 0.027) compared the HC. When responses to PPD were compared, proliferation of PMBC was lower (P = 0.03), whereas IL-12 secretion was higher in BD (P = 0.04) as well as in patients under colchicum treatment (P = 0.04) and with vascular involvement (P = 0.006) compared to HC. BES-1(373-385 )peptide induced also higher IL-12 productions by PBMC of BD patients (P = 0.017) and of patients with uveitis (P = 0.013). Finally, IPP stimulated higher IL-12 secretions from PBMC in BD patients (P = 0.035) and in patients with (P = 0.02) or without (P = 0.017) uveitis or arthritis (P = 0.04), under colchicum treatment (P = 0.01) or not receiving any immunosuppressive treatment (P = 0.007) compared to HC. These results suggest a more prominent pro-inflammatory cytokine secretion from PBMC in BD patients compared to HC in response to various antigens including alphaBC protein, BES-1(373-385), IPP and PPD.