Tcri

CTL I Allo-MHC

Naive CD4+ T cell

Antibody secreting plasma cell ft ^ ^ B cell

Antibody production

ADCC cytotoxicity

CTL I Allo-MHC

FcyR

Allo-antigen

FcyR

A. Recognition of self-class II MHC /microbial peptide complex

Microbial peptide Recipient's T cell

Self-MHC TCR Class I'

Typical antigen recognition

B. Direct Recognition of Graft: Allo-Class II MHC

Recipient's T cell

Recognition of graft antigen

C. Indirect Recognition of Graft: Self-Class II MHC/Allo-Class II MHC Peptide Complex

Antigen (Fragment- allo-class II MHC)

Recipient's T cell

Recognition of graft antigen

Self-MHC TCR Class II

Fig. 17.12. CD4+ allo-recognition compared with microbial antigen recognition. CD4+ T cells recognize antigen presented by self-class II MHC. They can recognize allo-class II MHC directly if allo-class II MHC mimics self-class II MHC plus antigen. Donor class II MHC expressing cells include dendritic cells, B-cells, mononuclear phagocytes, and vascular endothelium. CD4+ T cells may also recognize fragments of shed allo-class II MHC presented by self-class II MHC on host cells (indirect recognition).

Role of CD8+ T cells in graft rejection

CD8+ T cells, differentiating to CTL in the presence of Th1-derived IL-2, are important in graft destruction. Detailed analysis of CD8+ CTL indicates that most CTLs recognize allo-class I MHC directly, i.e., that allo-class I MHC mimics foreign antigen/self-class I MHC (Fig. 17. 13). Some CD8+ T cells are activated following recognition of self-class I MHC with donor-derived peptide. The mechanism(s) involved are not clear, though it is known that "empty" class I MHC on a cell surface can be "pulsed" with soluble peptide. Thus so-called INDIRECT allo-recognition can be documented for CD8+ T cells, though it is likely of much less

A. Recognition of self-class I MHC I viral peptide complex

Self-class I MHC TCR

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