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

K Honjo, X yan Xu, RP Bucy - Transplantation, 2004 - journals.lww.com
K Honjo, X yan Xu, RP Bucy
Transplantation, 2004journals.lww.com
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 TCRα and TCRβ chains that recognize
the K d 54–68/IA b epitope. Two different TCR Tg lines were produced in C57BL/6 (B6) mice …
Abstract
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 TCRα and TCRβ chains that recognize the K d 54–68/IA b epitope. Two different TCR Tg lines were produced in C57BL/6 (B6) 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 II is sufficient to activate TCR Tg T cells and serve as a target for rejection.
Lippincott Williams & Wilkins