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 HYDb 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 HYAb Dby peptide, NAGFNSNRANSSRSS, causes immunization similar to that following injection of male cells. Tolerance induced by HYDb Uty peptide pretreatment is not characterized by clonal deletion: long-term tolerant mice maintain circulating HYDb 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 HYDb 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.