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, thus facilitating immune surveillance against infected or cancerous cells. They are also involved in the regulation of immune responses [2,4-7]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying H2-K1 function.

In lung injury research, a subpopulation of club-like lineage-negative epithelial progenitors marked by high H2-K1 expression was found to be critical for alveolar repair. These quiescent H2-K1high cells have in vitro regenerative activity of airway lineages, and after bleomycin injury, they expand and differentiate in vivo to alveolar lineages, though injured cells eventually show impaired self-renewal [1].

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

In Alzheimer's disease and aging studies, microglial H2-K1 expression was found to increase with age and in AD mouse models and human AD data, suggesting an association with cellular senescence [4].

In colon cancer, IL11/STAT3 signaling downregulates H2-K1 expression, and its inhibition increases H2-K1 expression and CD8+ T cell infiltration [5]. In aggressive cancers, VSIG4+ tumor-associated macrophages with VSIG4 deficiency show recovered H2-k1-mediated antigen presentation and activated antigen-specific CD8+ T cells [6].

In melanoma and breast cancer models, deletion of Ndufs4 (a mitochondrial respiratory complex I subunit) induces H2-K1 expression, restricting tumor growth and increasing T cell surveillance [7].

In cerebral infection with Toxoplasma gondii, IFN-γ produced by brain-resident cells upregulates H2-K1 expression, facilitating protective T cell immunity [8].

In conclusion, H2-K1 is essential for immune-related functions, including antigen presentation and immune surveillance. Studies using KO or CKO mouse models have revealed its roles in various disease conditions such as lung injury, cancer, Alzheimer's disease, and cerebral infections. Understanding H2-K1 function provides insights into disease mechanisms and potential therapeutic strategies.