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Mechanisms of antigen presentation to T cells in murine graft-versus-host disease: cross-presentation and the appearance of cross-presentation. Blood 2011 Dec 08;118(24):6426-37

Date

10/04/2011

Pubmed ID

21963602

Pubmed Central ID

PMC3236124

DOI

10.1182/blood-2011-06-358747

Scopus ID

2-s2.0-83455219332   34 Citations

Abstract

Recipient antigen-presenting cells (APCs) initiate GVHD by directly presenting host minor histocompatibility antigens (miHAs) to donor CD8 cells. However, later after transplantation, host APCs are replaced by donor APCs, and if pathogenic CD8 cells continue to require APC stimulation, then donor APCs must cross-present host miHAs. Consistent with this, CD8-mediated GVHD is reduced when donor APCs are MHC class I(-). To study cross-presentation, we used hosts that express defined MHC class I K(b)-restricted miHAs, crossed to K(b)-deficient backgrounds, such that these antigens cannot be directly presented. Cross-priming was surprisingly efficient, whether antigen was restricted to the hematopoietic or nonhematopoietic compartments. Cross-primed CD8 cells were cytolytic and produced IFN-γ. CD8 cells were exclusively primed by donor CD11c(+) cells, and optimal cross-priming required that they are stimulated by both type I IFNs and CD40L. In studying which donor APCs acquire host miHAs, we made the surprising discovery that there was a large-scale transfer of transmembrane proteins from irradiated hosts, including MHC class I-peptide complexes, to donor cells, including dendritic cells. Donor dendritic cells that acquired host MHC class I-peptide complexes were potent stimulators of peptide-specific T cells. These studies identify new therapeutic targets for GVHD treatment and a novel mechanism whereby donor APCs prime host-reactive T cells.

Author List

Wang X, Li H, Matte-Martone C, Cui W, Li N, Tan HS, Roopenian D, Shlomchik WD

Author

Weiguo Cui PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antigen Presentation
Antigen-Presenting Cells
Autoantigens
Bone Marrow Transplantation
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cross-Priming
Dendritic Cells
Graft vs Host Disease
Histocompatibility Antigens Class I
Interferon-gamma
Mice
Mice, Inbred BALB C
Mice, Inbred Strains
Mice, Knockout
Mice, Transgenic
Minor Histocompatibility Antigens
Molecular Targeted Therapy
Peptide Fragments
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75