The role of indirect recognition of MHC class I and II allopeptides in a fully mismatched miniature swine model of lung transplantation.
Considerable evidence suggests that indirect recognition of MHC allopeptides plays an important role in solid-organ rejection. Here, we examine whether immunization with class I or class II allopeptides accelerates rejection in a fully MHC-mismatched lung transplant model in miniature swine.


METHODS
Recipients were immunized with either donor-derived class I or class II peptides. Sensitization to the peptides was confirmed by DTH testing and in vitro proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n = 3), and class II peptide-immunized (n = 3) swine were transplanted with fully mismatched lungs using only a 12-day course of tacrolimus.


RESULTS
One control animal rejected its graft on postoperative day 103, while the others maintained their grafts for over 1 year. In the class I peptide-immunized group, two recipients rejected their grafts (days 14 and 52). The third animal has not rejected the graft (day 120, experiment is ongoing). In contrast, in the class II-peptide immunized group, only one animal rejected its graft on day 52, while the others maintained their grafts over 1 year. Both anti-donor IgM and IgG antibodies were detectable in all acute rejectors, although no alloantibody was detectable in long-term acceptors. Regardless of the fate of the graft, all animals have maintained their proliferative responses to the peptides. However, only acceptors maintained donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity and mixed lymphocyte reaction assays.


CONCLUSIONS
Pretransplant sensitization of lung allograft recipients to donor allopeptides accelerates graft rejection. This appears particularly true for class I-derived allopeptides, suggesting that class II molecules may be less antigenic when presented indirectly.
Sahara
H
H
Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Shoji
T
T
Ng
C Y
CY
Weiss
M J
MJ
Muniappan
A
A
Guenther
D A
DA
Houser
S L
SL
Pujara
A C
AC
Sayre
J K
JK
Wain
J C
JC
Sachs
D H
DH
Madsen
J C
JC
Allan
J S
JS
D000818:Animals; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006650:Histocompatibility Testing; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016040:Lung Transplantation / Q000276:immunology*; D008285:Major Histocompatibility Complex; D023421:Models, Animal; D013552:Swine; D013556:Swine, Miniature
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M