Major histocompatibility complex class I antigen (MHC class I)

Major histocompatibility complex class I antigen is a heterodimeric, membrane-anchored glycoprotein present on all nucleated cells (and platelets) in vertebrates, but not on red blood cells[1][2][3][6]. It consists of an α (heavy) chain encoded by the HLA-A, HLA-B, or HLA-C genes (in humans) and a non-polymorphic β2-microglobulin chain[2][5]. The α chain forms a peptide-binding groove that accommodates short peptides (8–10 amino acids), derived from degraded endogenous or, less commonly, cross-presented exogenous proteins[3][2]. The assembled complex presents these peptide antigens at the cell surface, where they may be recognized by cytotoxic CD8+ T cells, triggering immune-mediated killing of infected or abnormal (e.g., cancerous) cells[2][3][5]. MHC class I molecules are critical for anti-viral and anti-tumor immunity and represent key determinants in the success or failure of organ transplantation and the outcome of certain immunotherapies[3][6]. Defects or dysregulation in MHC class I antigen expression are implicated in immune evasion by tumors, viral persistence, and autoimmune disorders[4]. Their expression level serves as a clinically relevant biomarker for predicting efficacy of immune-based cancer therapies and risk stratification in transplantation.

Other names

HLA class I (in humans)HLA-AHLA-BHLA-CMHC-I

Enhancing or blocking antigen presentation to cytotoxic T cells (drugs modulate this, but none directly bind MHC class I). Immune checkpoint inhibitors restore T cell recognition of tumor-associated MHC class I–presented antigens. Some therapies target peptide loading or immunoproteasome activity, affecting MHC class I antigen repertoire and presentation.