Cutting Edge: Roles for Batf3-Dependent APCs in the Rejection of Minor Histocompatibility Antigen-Mismatched Grafts

J Immunol. 2015 Jul 1;195(1):46-50. doi: 10.4049/jimmunol.1500669. Epub 2015 Jun 1.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • Gene Expression Regulation, Developmental*
  • Graft Rejection*
  • Histocompatibility Testing
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Male
  • Mice
  • Mice, Knockout
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / immunology*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Signal Transduction
  • Skin Transplantation*
  • Spleen / cytology
  • Spleen / immunology
  • Transplantation, Homologous

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Minor Histocompatibility Antigens
  • Repressor Proteins
  • SNFT protein, mouse