title: Cutting Edge: Roles for Batf3-Dependent APCs in the Rejection of Minor Histocompatibility Antigen-Mismatched Grafts.
abstract: In transplantation, a major obstacle for graft acceptance in MHC-matched individuals is the mismatch of minor histocompatibility Ags. Minor histocompatibility Ags are peptides derived from polymorphic proteins that can be presented by APCs on MHC molecules. The APC subtype uniquely responsible for the rejection of minor Ag-mismatched grafts has not yet been identified. In this study, we examined graft rejection in three mouse models: 1) mismatch of male-specific minor Ags, 2) mismatch of minor Ags distinct from male-specific minor Ags, and 3) skin transplant. This study demonstrates that in the absence of pathogen-associated molecular patterns, Batf3-dependent dendritic cells elicit the rejection of cells and grafts expressing mismatched minor Ags. The implication of our findings in clinical transplantation may be significant, as minor Ag reactivity has been implicated in the pathogenesis of multiple allograft tissues.
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO 80206;
authors.forename: Shaikh M
authors.initials: SM
authors.lastname: Atif
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80206;
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Nelsen
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO 80206;
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Gibbings
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80206;
authors.forename: A Nicole
authors.initials: AN
authors.lastname: Desch
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO 80206;
authors.forename: Ross M
authors.initials: RM
authors.lastname: Kedl
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO 80206;
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Gill
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80206; Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Howard Hughes Medical Institute, Denver, CO 80206; and.
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
authors.affiliation: Howard Hughes Medical Institute, Denver, CO 80206; and Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63130.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80206;
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Grazia
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80206;
authors.forename: Peter M
authors.initials: PM
authors.lastname: Henson
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80206; jakubzickc@njhealth.org.
authors.forename: Claudia V
authors.initials: CV
authors.lastname: Jakubzick
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006084:Graft Rejection; D006650:Histocompatibility Testing; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C533289:SNFT protein, mouse