Fig. 1. Various mechanisms of allorecognition of T cells. Mature APCs activate CD4+ and CD8+ T cells by presenting donor-derived peptides via MHC molecules through three pathways: direct, indirect, and semidirect. (A) In the direct pathway, recipient T cells recognize donor MHC-peptide complexes on donor APCs, and CD8+ T cells are assisted by CD4+ T cells. (B) In the indirect pathway, CD4+ T cells interact with recipient MHCs presenting peptides from processed donor MHCs. Meanwhile, ⓐ CD8+ T cells interact with recipient APCs via cross-presentation (three-cell model) or ⓑ donor APCs (four-cell model) and receive assistance from CD4+ T cells. (C) The semidirect pathway involves CD8+ T cells recognizing intact donor MHC class I on recipient APCs and receiving assistance from CD4+ T cells that recognize recipient MHC class II with processed peptides on recipient APCs. APC, antigen-presenting cell; MHC, major histocompatibility complex; TCR, T cell receptor; IL, interleukin.