Rapid rejection of HLA-A2 transgenic skin graft due to indirect allorecognition.
BACKGROUND
At present, it is not clear whether xenogeneic MHC molecules are recognized by T cells directly or indirectly through self-MHC-restricted presentation in a transplantation setting.


METHODS
We have transplanted skin from HLA-A2 transgenic (B6.A2) to nontransgenic C57BL/6 (B6) mice and investigated the subsequent mouse T-cell responses to HLA molecules, in vivo and in vitro.


RESULTS
Skin transplanted from transgenic B6.A2 to B6 mice was rejected rapidly, in 12-16 days. Although naive B6 mice did not respond to B6.A2 splenocytes in vitro, spleen cells from mice that underwent transplantation showed strong proliferative responses. An anti-B6.A2 T-cell line from mice that underwent transplantation made proliferative responses to B6.A2 splenocytes but did not recognize HLA-A2 on human cells or transfected allogeneic mouse cells. The indirect, self-H-2-restricted recognition of HLA-A2 implied by this was confirmed by the finding that lysates of HLA-A2-positive, but not HLA-A2-negative, human B cells were stimulatory when pulsed onto syngeneic antigen-presenting cells and by inhibition of anti-B6.A2 proliferation with both anti-mouse MHC class I and class II antibodies.


CONCLUSIONS
Our results suggest that indirect recognition of xenogeneic MHC antigen plays a predominant role in graft rejection.
Jurcevic
S
S
Department of Nephrology & Transplantation, King's College, Guy's, King's and St. Thomas' Medical School, Guy's Hospital, London SE1 9RT, UK. stipo.jurcevic@kcl.ac.uk.
Chandler
P
P
Sacks
S H
SH
Simpson
E
E
D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology; D002455:Cell Division; D006084:Graft Rejection / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D017634:Self Tolerance / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D019076:Transgenes / Q000502:physiology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
D000910:Antibodies, Heterophile; D015789:HLA-A2 Antigen