HLA-DQA1 antibodies target the alpha chain of the HLA-DQ heterodimer, a class II major histocompatibility complex (MHC) molecule encoded by the HLA-DQA1 gene. These molecules are critical for immune regulation, as they present exogenous peptide antigens to CD4+ T cells to initiate adaptive immune responses. HLA-DQ molecules consist of an α-chain (HLA-DQA1) and a β-chain (HLA-DQB1), both of which exhibit high polymorphism, influencing antigen-binding specificity and disease susceptibility. Antibodies against HLA-DQA1 are less commonly studied compared to those targeting HLA-DQβ or HLA-DR, but they hold clinical significance in transplantation and autoimmune disorders. In organ transplantation, preformed or de novo HLA-DQA1 antibodies may contribute to graft rejection by triggering complement activation or antibody-dependent cellular cytotoxicity. Additionally, certain HLA-DQA1 alleles are strongly associated with autoimmune conditions like celiac disease (e.g., DQA1*05:01) and type 1 diabetes (e.g., DQA1*03:01), where autoantibodies may arise against tissue-specific antigens in genetically predisposed individuals. Research also explores HLA-DQA1 antibodies as potential biomarkers for disease risk stratification or therapeutic monitoring. However, their detection and interpretation remain technically challenging due to the complexity of HLA-DQ epitopes and cross-reactivity with other HLA class II molecules. Advances in epitope mapping and high-resolution HLA typing continue to refine understanding of their pathophysiological roles.