Indirect T cell allorecognition of donor antigens contributes to the rejection of vascularized kidney allografts.
This report demonstrates for the first time that indirect T cell allorecognition of donor antigens can contribute to the effector mechanism of rejection of vascularized organ allografts. LEW (RT1(1)) rats were primed for indirect T cell allorecognition of DA (RT1av1) classical class I MHC molecules by immunization with synthetic 22-24 amino acid peptides corresponding to the alpha-helices of the RT1-A class I molecule. These rats received (DA x LEW) F1 kidney grafts that had been depleted of donor interstitial dendritic cells to minimize the direct T cell allorecognition response to the graft. The peptide-immunized rats rejected their grafts more rapidly than did control immunized rats, in terms of both graft function and survival. Moreover, the kinetics of antibody production to intact donor class I molecules after kidney transplantation was much more rapid in the peptide-immunized rats, suggesting that T cell help is the rate-limiting factor for antibody production to donor antigens in this model. It was of interest that we could not detect an antibody response to donor peptides after kidney graft rejection.
Benham
A M
AM
Transplantation Biology Unit, University of London, United Kingdom.
Sawyer
G J
GJ
Fabre
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D007519:Isoantigens; D010455:Peptides