Naive spleen cells from DR1-T cell receptor (TCR) Tg mice respond to culture with type II collagen (CII). Spleen cells from naive DR1-TCR Tg mice were cultured with human A2, murine A2, A12 or bovine α1(II) chains with titrated doses. Cytokines are expressed as pg/ml. Proliferation was measured by incorporation of (3H)-thymidine and is expressed as the mean disintegrations per minute (dpm) of triplicate cultures. Data are expressed as means ± standard error of the mean of experiments using three separate mice. Responses to the murine determinant differ significantly from those induced to either human A2 or bovine α1(II) when comparing proliferation, IFN-γ, IL-17, or IL-10 (P ≤0.05 using the Mann–Whitney test). Responses to A12 differ significantly from the responses to human A2, α 1(II) and murine A2 in proliferation, IFN- γ and IL-17 (P ≤0.05 using the Mann–Whitney test) but the A12-induced IL-10 response was not different.