Figure 1.

Hypothesis of the induction of a T cell mimicry response leading to ocular autoimmunity. (A) Outside of the eye in the body (gut)?: A naive T cell has first contact with a non-eye-related antigen. In case of a concomitant danger signal (injury of the tissue, infection) innate antigen-presenting cells (APCs) are activated to induce effector T cell responses. (B) The antigen recognized by the T cell can either be from a pathogen [from infection or a food antigen, see (A)]. If the T cell recognizes harmless food antigen and erroneously receives concomitant activation signals from the APC alerted by danger signals the T cell gets activated and differentiates into a T helper (e.g. here: Th1) cell. (C) Activated T cells migrate in the blood circulation. In search of their antigen they can leave the blood vessels and enter even immune privileged organs like the eye. (D) The triangles represent retinal autoantigen peptides presented on MHC class II. The precise signals of attracting a T cell to a certain organ at a certain site (blood vessel) are still unknown. (E) When the T cell has screened the eye and found an antigen binding to its receptor, it gets reactivated and secretes cytokines and chemokines to recruit inflammatory cells. The intraocular antigen is different to the antigen of the original T cell priming outside of the eye. (F) Innate cells (monocytes/macrophages and/or granulocytes) recruited from the circulation are causing inflammation and tissue destruction resulting in uveitis. (G) Two different peptides presented and recognized by the same HLA molecule and T cell receptor (TCR), despite their restricted homologies. Only the core sequence of 8 amino acids presented in the groove is shown. Identical amino acid side chains are marked by white asterisks, the arrows point to similar side chains representing different amino acids also anchoring to the presenting HLA-molecule or being bound by the TCR.