CD4+T-cell receptor transgenic T cells alone can reject vascularized heart transplants through the indirect pathway of alloantigen recognition

The vast array of epitopes presented by allografts and the diversity of T cells responding to them complicates mechanistic studies of rejection. To minimize these problems, we developed a transgenic (Tg) model system limited to a single T-cell receptor (TCR)/peptide/major histocompatibility complex molecule. Two alloantigen-specific CD4 T-cell clones were used to isolate cDNA encoding the TCRalpha and TCRbeta chains that recognize the K-54-68(d)/I-A(b) epitope. Two different TCR Tg lines were produced in C57BL/6 (136) mice and crossed onto the B6.Rag1(-/-) background. B6.Rag1(-/-) recipients of T cells from TCR Tg Rag1(-/-)mice promptly rejected B10.D2, but not irrelevant B10.BR, cardiac grafts. Thus, a single allogeneic epitope presented by self-major histocompatibility complex class 11 is sufficient to activate TCR Tg T cells and serve as a target for rejection.