HLA-DQA2

Description

The HLA-DQA2 (major histocompatibility complex, class II, DQ alpha 2) is a protein-coding gene located on chromosome 6.

HLA class II histocompatibility antigen, DQ(6) alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leukocyte antigen system. The protein encoded by this gene is expressed, but unlike HLA-DQA1, it is apparently unable to heterodimerize with HLA class II beta chain paralogues. The low level of HLA-DQA2 expression is apparently due to impaired transcription factor binding to the HLA-DQA2 gene promoter. Transcriptome analysis of blood immune cells and nasopharyngeal cells before elaborate infection of study participants revealed that heightened expression of HLA-DQA2 correlates to a significantly lower chance of COVID-19 successfully infecting the individual.

HLA-DQA2, also known as DX alpha chain, is a component of the MHC class II molecule, which presents antigens to CD4 T-cells. It forms a heterodimer with HLA-DQB2, but not with HLA-DQB1, and this dimerization is crucial for its exit from the endoplasmic reticulum. In the ER, three MHC class II molecules associate with a CD74 trimer (invariant chain) to form a heterononamer. During its transport to endosomes and lysosomes for antigen processing, CD74 is sequentially degraded, leaving a small fragment called CLIP on each MHC class II molecule. HLA-DM and HLA-DO (in B cells and dendritic cells) facilitate the release of CLIP and the binding of antigenic peptides. This process is influenced by the lysosomal microenvironment, with increased acidification enhancing proteolysis and peptide loading. HLA-DQA2 plays a critical role in antigen presentation by presenting peptides derived from exogenous antigens that have been endocytosed by antigen-presenting cells (APCs). These peptides are generated by lysosomal proteases and other hydrolases. HLA-DQA2 also presents peptides derived from autophagy, where autophagosomes fuse with MHC class II loading compartments.

HLA-DQA2 is also known as DC-alpha, DQA1, DX-ALPHA, HLA-DCA, HLA-DXA, HLADQA2.

Associated Diseases

WES Whole Exome Sequencing