In indirect allorecognition, which mechanism describes how donor-derived peptides are presented to recipient T cells?

• A. Processed peptides from polymorphic donor proteins restricted by recipient HLA class II molecules
• B. Processed peptides from polymorphic recipient proteins restricted by donor HLA class I molecules
• C. Intact polymorphic donor protein molecules recognized by recipient HLA class I molecules
• D. Intact polymorphic donor protein molecules recognized by recipient HLA class II molecules

Answer: (A)

Indirect allorecognition involves the recipient’s antigen-presenting cells taking donor-derived polymorphic proteins, processing them into peptides, and presenting those peptides on the recipient’s HLA class II molecules to CD4+ T helper cells. This is why the description of processed peptides from donor proteins restricted by recipient HLA class II molecules is the best fit. It contrasts with direct recognition, where recipient T cells see intact donor MHC-peptide complexes presented by donor APCs (often involving donor class I or II MHC), and with ideas about intact donor proteins being recognized, which does not characterize the indirect pathway.