**4.4 Indirect pathway**

In the indirect pathway, T cells recognize processed alloantigens that are presented as peptides by self-APCs. Secondary responses such as those that occur in chronic or late acute rejection are associated with T cell proliferative responses to a more variable repertoire, including peptides that were previously immunologically silent. Such a change in the pattern of T cell responses has been termed epitope switching or spreading.

A link between self-MHC + allopeptide-primed T cells and the development of acute vascular rejection has been demonstrated to be mediated in part by accelerated alloantibody production. In addition, chronic allograft vasculopathy may be mediated by T cells primed by the indirect pathway[11].
