Figure 1.

Three different ways resting/naïve T lymphocytes become activated. Activation by the first encounter requires naïve lymphocytes associated with professional antigen-presenting cells, namely, dendritic cells. The second encounter with the antigen is enough to generate a fast, strong response for memory lymphocytes in the resting state. Hypotheses based on the canonical first/second encounter models led to an exploration of potential cross-reactive antigens that elicit spondyloarthritis after pathogen infection. With improved knowledge of the immune regulatory network, the antigen-independent activation of T cells has been identified, which provides a possible pathway for autoreactive T cells that bypasses central tolerogenesis mechanisms.