Graft-specific MHC class II gene expression in response to allogeneic stimulus in heterotopiic murine cardiac allografts

Although, major histocompatibility complex (MHC) class II antigen expression in allografts is thoroughly studied, regulation of the genes for these antigens is not fully understood. The graft-specific MHC class II genes are potentially important in determining the immunogenicity of graft but their detection in a mixed-cell population such as in the allograft would require unambiguous differentiation of graft-specific class II expression from those in host lymphoid cells. With an oligonucleotide probe that specifically hybridizes to I-Ab mRNA from H-2(k) haplotype mice, we have studied I-A gene expression in cardiac allografts heterotopically transplanted from B10.Br (H-2(k)) to B10.D2 (H-2(d)) mice. Normal B10.Br hearts do not have appreciable I-Ab transcripts as determined with this probe, but 4 days after allografting, a substantial increase in I-Ab(k) messenger RNA (mRNA) content was noted in the allografted hearts which persisted for the next 2 days and then decreased concomitant with destruction of the heart. The increase in I-Ab(k) mRNA preceded the expression of surface Ia(k) antigens on dendritic and endothelial cells in the allograft. These data indicate increased transcription of the I-Ab gene in cells of graft origin suggesting that transcriptional regulation is the initial mechanism for expression of class II genes in allografts. The sustained rise in graft-specific class II mRNA also seen in these allografts suggests that increased mRNA stability may be another mechanism for the increased density of class II antigens in allografts undergoing rejection.