Primary vascularization of the graft determines the immunodominance of murine minor H antigens during organ transplantation. J Immunol 2011 Oct 15;187(8):3997-4006
Date
09/09/2011Pubmed ID
21900176Pubmed Central ID
PMC3357205DOI
10.4049/jimmunol.1003918Scopus ID
2-s2.0-80054733899 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Grafts can be rejected even when matched for MHC because of differences in the minor histocompatibility Ags (mH-Ags). H4- and H60-derived epitopes are known as immunodominant mH-Ags in H2(b)-compatible BALB.B to C57BL/6 transplantation settings. Although multiple explanations have been provided to explain immunodominance of Ags, the role of vascularization of the graft is yet to be determined. In this study, we used heart (vascularized) and skin (nonvascularized) transplantations to determine the role of primary vascularization of the graft. A higher IFN-γ response toward H60 peptide occurs in heart recipients. In contrast, a higher IFN-γ response was generated against H4 peptide in skin transplant recipients. Peptide-loaded tetramer staining revealed a distinct antigenic hierarchy between heart and skin transplantation: H60-specific CD8(+) T cells were the most abundant after heart transplantation, whereas H4-specific CD8(+) T cells were more abundant after skin graft. Neither the tissue-specific distribution of mH-Ags nor the draining lymph node-derived dendritic cells correlated with the observed immunodominance. Interestingly, non-primarily vascularized cardiac allografts mimicked skin grafts in the observed immunodominance, and H60 immunodominance was observed in primarily vascularized skin grafts. However, T cell depletion from the BALB.B donor prior to cardiac allograft induces H4 immunodominance in vascularized cardiac allograft. Collectively, our data suggest that immediate transmigration of donor T cells via primary vascularization is responsible for the immunodominance of H60 mH-Ag in organ and tissue transplantation.
Author List
Kwun J, Malarkannan S, Burlingham WJ, Knechtle SJAuthor
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD8-Positive T-Lymphocytes
Chemotaxis, Leukocyte
Chromatography, High Pressure Liquid
Graft Rejection
Heart Transplantation
Immunodominant Epitopes
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Minor Histocompatibility Antigens
Neovascularization, Physiologic
Skin Transplantation
Transplantation, Homologous
