HLA-DRA encodes the alpha chain of the MHC class II DR molecule, which partners with HLA-DRB to present antigenic peptides to CD4+ T cells for immune recognition 1. The protein functions as a critical component in antigen presentation, displaying peptides of 10-30 amino acids derived from endocytosed antigens processed in lysosomes. In disease contexts, HLA-DRA expression serves as an activation marker on T cells, with nearly one-third of coronary plaque T cells expressing HLA-DRA, indicating TCR-mediated activation 1. These activated T cells show clonal expansion and cross-reactivity to viral and self-antigens, potentially contributing to autoimmune processes in atherosclerosis 1. HLA-DRA expression is prognostically significant across multiple conditions: reduced expression in peripheral blood CD14+ cells predicts severe COVID-19 outcomes as early as four days before respiratory decline 2, while elevated expression occurs in osteoarthritis and unstable atherosclerotic plaques, correlating with inflammatory immune infiltration 34. Genetic variants in HLA-DRA show association with alcohol dependence in Caucasian populations 5. The gene's transcription is tightly regulated through tissue-specific and cytokine-inducible mechanisms involving multiple transcription factor families 6. Therapeutically, HLA-DRA represents a potential drug target, with Mendelian randomization suggesting its downregulation may reduce sarcopenia risk 7.