H2-K1 is a gene encoding a major histocompatibility complex class I (MHC-I) molecule in mice. MHC-I molecules play a crucial role in the immune system by presenting peptide antigens to cytotoxic T cells, which is essential for the recognition and elimination of infected or cancerous cells. They are also involved in immune surveillance and maintaining immune homeostasis [2,4,5,6,7,8,9]. Genetic models, such as KO or CKO mouse models, are valuable tools for studying H2-K1's function.

In lung injury models, a subpopulation of club-like lineage-negative epithelial progenitors marked by high H2-K1 expression was found to be critical for alveolar repair. However, injured H2-K1 cells develop impaired self-renewal and senescence, limiting complete repair. Transplanting normal H2-K1high cells can rescue lung function [1].

In cancer research, engineering an inducible affinity tag into the H2-K1 gene enabled the isolation of MHC-I peptides from pancreatic and lung adenocarcinomas in vivo, helping to identify new tumor antigens [2]. Additionally, H2-K1 protects murine MLL-AF9 leukemia stem cells from natural killer cell-mediated immune surveillance [3].

In Alzheimer's disease and aging models, microglial H2-K1 expression increases, and it may be associated with cellular senescence [4].

In cancer models, IL11/STAT3 signaling downregulates H2-K1 expression, and its inhibition increases MHC-I expression and T-cell infiltration [5].

Retinal microglia express more H2-K1 than brain microglia, potentially enhancing CD8+ T-cell inflammation during viral infection [6].

VSIG4+ tumor-associated macrophages with VSIG4 deficiency recover H2-K1-mediated antigen presentation and activate antigen-specific CD8+ T cells [7].

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 induces H2-K1 expression, increasing tumor immunogenicity [8].

In the context of Toxoplasma gondii infection, IFN-γ produced by brain-resident cells upregulates H2-K1 expression to facilitate T-cell-mediated protective immunity [9].

In conclusion, H2-K1 is essential for immune-related functions, including antigen presentation, immune surveillance, and cellular repair. Mouse models with H2-K1 gene manipulations have provided insights into its role in lung injury repair, cancer immune evasion, Alzheimer's disease, and infectious diseases. These findings contribute to our understanding of the underlying mechanisms and suggest potential therapeutic targets for related diseases.