HLA class I histocompatibility antigen, C alpha chain (HLA-C) (HLA-C)

HLA class I histocompatibility antigen, C alpha chain (HLA-C) is a critical component of the human major histocompatibility complex (MHC) class I system, essential for both innate and adaptive immunity [1, 2]. It functions as a heterodimer that presents endogenous peptides to CD8+ cytotoxic T cells, enabling the immune system to identify and destroy virally infected or neoplastic cells [1]. Additionally, HLA-C serves as a primary ligand for Killer-cell Immunoglobulin-like Receptors (KIRs) on Natural Killer (NK) cells, where it typically delivers inhibitory signals to maintain self-tolerance and prevent autoimmunity [4]. Genetic variations in HLA-C, such as the HLA-C*06:02 allele, are strongly linked to the pathogenesis of psoriasis, while expression levels of the molecule influence the clinical progression of HIV-1 [3, 4]. In oncology, HLA-C is a target for novel immunotherapies, including TCR-T cell therapies designed to recognize specific mutations like KRAS G12D when presented by particular HLA-C alleles [6]. Therapeutic modulation of the HLA-C/KIR axis, such as with the antibody lirilumab, aims to unleash NK cell activity against tumors by blocking inhibitory interactions [5].

Other names

HLA-CMHC class I antigen CHLA-CwPSORS1Major histocompatibility complex, class I, C

Enhancement of NK cell-mediated cytotoxicity via KIR receptor blockade and induction of antigen-specific T-cell responses through peptide-MHC presentation [5, 6].