Treatment with either A12-immune cells or A12 peptide can suppress arthritis. Panel A: CD4+ T cells from the double transgenic mice treated with A12 can transfer the suppression of arthritis. Single-transgenic DR1 mice (10/group) were infused with 5 × 105 cells of A12-primed CD4+ T cells from double-transgenic mice or Ova-primed CD4+ T cells from single-transgenic DR1 mice. Recipient animals were immunized with bovine type II collagen (bCII)/CFA and observed for arthritis. Only A12-immune cells prevented collagen-induced arthritis (final severity scores 1.0 ± 0.5 versus 7.4 ± 1.2, P ≤0.0001; final incidence 90% versus 10% in the treatment group). (Panel B) Oral treatment with peptide A12 (prevention protocol). Groups of 12 double-transgenic mice were administered PBS or A12 peptide (oral gavage three times/week), beginning the day after immunization with bCII/CFA, continuing for the duration of the experiment. On day 46, mice fed PBS had a severity score of 4.5 ± 0.4, which differed from mice fed 10 μg of A12 (2.4 ± 0.5, P ≤0.05) and mice fed 50 μg of A12 (1.5 ± 0.04, P ≤0.01; final incidence = 80% in the control and 20% in the 50-μg group). (Panel C) Oral treatment with peptide A12 (treatment protocol). Groups of 10 double-transgenic mice were administered PBS or A12 peptide (50 μg/dose, oral gavage three times/week) beginning the day of arthritis onset. On day 46, mice fed PBS had a severity score of 6.8 ± 0.6, which differed from mice fed 50 μg of A12 (3.6 ± 0.4, P ≤0.05) (Mann–Whitney test). (Final incidence = 90% in controls and 60% in the treatment group).