HY peptides modulate transplantation responses to skin allografts.
Injection of female C57BL/6 mice with immature female bone marrow-derived dendritic cells (BMDC) pulsed with a single immunodominant HY(Db) Uty peptide, WMHHNMDLI, induces prolonged survival of syngeneic male skin grafts. In contrast, injection of immature female BMDC pulsed with a single MHC class I-restricted HY(Ab) Dby peptide, NAGFNSNRANSSRSS, causes immunization similar to that following injection of male cells. Tolerance induced by HY(Db) Uty peptide pretreatment is not characterized by clonal deletion: long-term tolerant mice maintain circulating HY(Db) Uty tetramer(+) T cells which expand following exposure to male cells in vivo or in vitro. Tolerance to male skin grafts can be adoptively transferred into neonatal females with splenocytes from tolerant donors. Tolerance is specific-third-party skin grafts are rejected. We propose that tolerance in this model is initiated by cognate interaction of HY(Db) Uty-specific CD8(+) T cells with their ligand, presented either on the injected immature BMDC or on recipient DC. This interaction leads to incomplete activation of the CD8(+) T cells resulting in diminished responsiveness of CD4(+) and CD8(+) T cells specific for HY peptide epitopes subsequently presented on the male graft.
James
Edward
E
Transplantation Biology Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College of Science, Technology & Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Scott
Diane
D
Chai
Jian-Guo
JG
Millrain
Maggie
M
Chandler
Phillip
P
Simpson
Elizabeth
E
D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism / Q000637:transplantation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology; D066298:In Vitro Techniques; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D051379:Mice; D016038:Skin Transplantation / Q000276:immunology*
C051256:H-Y antibody; D007518:Isoantibodies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor