Development of a humanized HLA-A30 transgenic mouse model.

Area of Science:

• Immunology
• Genetics
• Transgenic animal models

Background:

• Significant genetic disparities exist between animal MHC and human HLA systems.
• Human leukocyte antigen (HLA) transgenic humanized mouse models are crucial for studying HLA-A-related mechanisms in vaccine development and immune responses to infection.

Purpose of the Study:

• To develop a novel humanized mouse model expressing a chimeric HLA-A30 monochain.
• To evaluate the utility of this model in studying immune responses to influenza A virus (H1N1) pdm09 infection.

Main Methods:

• A recombinant gene encoding a chimeric HLA-A30 monochain (HHD molecule) was constructed.
• The gene was integrated into a bacterial artificial chromosome (BAC) containing the HLA-A01 gene locus and microinjected into mouse oocytes.
• The resulting humanized mice were infected with H1N1 pdm09 to assess immune cell populations, cytokine production, and lung histopathology.

Main Results:

• A novel human β2m-HLA-A30 (α1α2)-H-2D^b (α3 transmembrane cytoplasmic) (HHD) monochain transgenic mouse strain was successfully established.
• Robust transgene expression was detected in multiple tissues, and the presence of the HLA-A gene locus influenced immune cell composition.
• Infection with H1N1 pdm09 induced similar immune responses and cytokine increases (IFN-γ, TNF-α, IL-6) in both humanized and wild-type mice, with enhanced HLA-A30 transgene expression post-infection.

Conclusions:

• A promising preclinical research animal model of HLA-A30 transgenic humanized mice has been established.
• This model can accelerate the identification of HLA-A30-restricted epitopes and aid in vaccine development.
• The model supports the study of HLA-A-restricted responses to human infections.