Improved Transgenic Mouse Model for Studying HLA Class I Antigen Presentation

Sci Rep. 2016 Sep 16;6:33612. doi: 10.1038/srep33612.

Abstract

HLA class I (HLA-I) transgenic mice have proven to be useful models for studying human MHC-related immune responses over the last two decades. However, differences in the processing and presentation machinery between humans and mice may have profound effects on HLA-I restricted antigen presentation. In this study, we generated a novel human TAP-LMP (hTAP-LMP) gene cluster transgenic mouse model carrying an intact human TAP complex and two human immunoproteasome LMP subunits, PSMB8/PSMB9. By crossing the hTAP-LMP strain with different HLA-I transgenic mice, we found that the expression levels of human HLA-I molecules, especially the A3 supertype members (e.g., A11 and A33), were remarkably enhanced in corresponding HLA-I/hTAP-LMP transgenic mice. Moreover, we found that humanized processing and presentation machinery increased antigen presentation of HLA-A11-restricted epitopes and promoted the rapid reduction of hepatitis B virus (HBV) infection in HLA-A11/hTAP-LMP mice. Together, our study highlights that HLA-I/hTAP-LMP mice are an improved model for studying antigen presentation of HLA-I molecules and their related CTL responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology*
  • Antiviral Agents / pharmacology
  • Epitopes, T-Lymphocyte / immunology
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity / drug effects
  • Membrane Transport Proteins / metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Animal
  • Peptides / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antiviral Agents
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Membrane Transport Proteins
  • Peptides
  • tapasin
  • Proteasome Endopeptidase Complex