Analysis of Type II Collagen Reactive T Cells in the Mouse

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Abstract
The specificity of the recognition of type II collagen (CII) by T cells in the DBA/l mouse was analysed using fragments of chick and rat CII obtained by cyanogen bromide (CB) cleavage. Firstly, DBA/l mice were immunized with chick CB fragments 5, 8, 9, 10, 11 and 12. Ten days later the draining lymph node cells were cultured with rat and mouse CII and the proliferative response was determined by incorporation of [3H]thymidine. All peptides were capable of triggering T cells recognizing rat CII but only CB9 immunized mice responded well to mouse CII. Secondly, lymph node cells from DBA/l mice immunized with rat and mouse CII were cultured with the CB fragments, including rat CB10 and CB11, and the proliferative response was determined. After immunization with rat CII, the response was strongly dominated by T cells recognizing CB11 with equal responses against chick and rat CB11. After immunization with mouse CII only rat CB10 gave a strong response. It is concluded that several epitopes on the CII molecule can be recognized by T cells in the DBA/l mouse and that most of these epitopes are shared by rat and chick CII but not mouse CII. These epitopes exhibit strong immunodominance. In mice immunized with intact heterologous CII, the immunodominant response is directed against one or more epitopes on the CB11 fragment present on several heterologous CII but apparently not on mouse CII. In mice immunized with autologous CII the immunodominant response is directed against one or more epitopes on the CB10 fragment, present on rat and mouse CII. They are either absent in chick CII or located in the carboxyterminal end of the CB10 fragment where a cyanogen bromide cleavage site is present in chick CII but not in rat CII. These results suggest that the proposed importance of CB11 in collagen-induced arthritis is due to activation of T cells reactive with heterologous CII only. These cells may be important for the induction of the strong auto-antibody-response after immunization with heterologous CII. Structures of importance for direct T cell involvement in the arthritic process and recognized by autoreactive T cells are suggested to be found on CB10.