Allorecognition in T-cell receptor (beta-chain) transgenic mice.
Recent advances in knowledge of the structure of the T-cell receptor and of major histocompatibility complex (MHC) molecules have increased our understanding of the nature of their interaction in the immune response. Nevertheless, it remains unclear how the T-cell receptor recognizes foreign MHC molecules in the process of graft rejection. One approach to this problem is to characterize the alloreactivity of a given T-cell receptor. We have chosen to take this approach in vivo by examining patterns of rejection of vascularized heart allografts in transgenic mice carrying a rearranged T-cell receptor-beta-chain gene, in which essentially all alpha beta T cells bear the rearranged gene product. Heterotopic heart allografts were performed in transgene-positive and transgene-negative recipients. The data show that transgene-positive mice will reject fully allogeneic grafts of three different haplotypes after a modest delay, but will not reject grafts from F1 mice that bear H-2 antigens from these same haplotypes and from the recipient strain. Transgene-negative animals reject all grafts promptly. These results suggest that the restricted T-cell receptor repertoire expressed by transgene-positive recipients affects their ability to respond to an alloantigen as expressed on a vascularized graft and that this response is influenced by the presence of self-MHC molecules on the graft.
Barrett
L V
LV
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Rimm
I J
IJ
Wiens
G R
GR
Seidman
J G
JG
Kirkman
R L
RL
D000818:Animals; D006084:Graft Rejection / Q000235:genetics; D006239:Haplotypes; D016027:Heart Transplantation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014184:Transplantation, Homologous / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta