HLA-DR Antibody (L243) [DyLight 550]

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Human Leukocyte Antigen -DR isotype (HLA-DR) is a major histocompatibility complex (MHC) class II molecule expressed by antigen presenting cells (APCs) that plays a significant role in immune response (1). Class II molecules also include isoforms HLA-DP and -DQ (1,2). These type I membrane glycoproteins on APCs present peptides to helper T cells and T cell receptors on CD4+ cells (1). In humans, the genes encoding class II MHC proteins are located on chromosome 6p21, where HLA-DR is typically the most highly expressed, followed by HLA-DQ and then HLA-DP (3). Structurally, HLA-DR molecules are heterodimers consisting of an alpha chain subunit with an approximate theoretical molecular weight of 34 kDa and one of many approximately 30 kDa beta subunits (1-3). The alpha and beta genes are considered highly polymorphic with duplication resulting in nine DRB (beta subunit of HLA-DR) genes (DRB1-DRB9); though only DRB1, DRB3, DRB4, and DRB5 are considered functional (2,3). On the other hand, the alpha subunit is encoded by a single DRA gene (2,3). Studies focusing on the structural and biochemical properties of peptides that bind to HLA-DR molecules have helped contribute to subunit vaccine design and development (3).

Given the role in adaptive immunity, HLA-DR allele polymorphisms, gene misexpression, and dysfunction has been implicated in many diseases ranging from autoimmune disorders to cancer (2). HLA-DR is also a classical biomarker for disease, including sepsis where reduced expression of HLA-DR molecules on monocytes, as measured by flow cytometry, indicates diagnosis and prognosis (4,5). Immunosuppression observed with sepsis results in decreased surface expression of HLA-DR and concurrent increase in expression of programmed death 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and B and T lymphocyte attenuator (BTLA) (4). This altered expression results in poor T cell response and apoptosis, along with reduced interferon-gamma (IFN-gamma) production and increased pro-inflammatory cytokine release (4). Furthermore, the decrease in HLA-DR expression is also correlated with the decrease in CD14lowCD16+ inflammatory monocytes (5). Interestingly, COVID-19 patients also exhibit a reduction in HLA-DR that correlates with disease severity and immunosuppression (5).

References

1. Andersson G. (1998). Evolution of the human HLA-DR region. Frontiers in bioscience : a journal and virtual library. https://doi.org/10.2741/a317

2. Shiina, T., Hosomichi, K., Inoko, H., & Kulski, J. K. (2009). The HLA genomic loci map: expression, interaction, diversity and disease. Journal of human genetics. https://doi.org/10.1038/jhg.2008.5

3. Stern, L. J., & Calvo-Calle, J. M. (2009). HLA-DR: molecular insights and vaccine design. Current pharmaceutical design. https://doi.org/10.2174/138161209789105171

4. Zhuang, Y., Peng, H., Chen, Y., Zhou, S., & Chen, Y. (2017). Dynamic monitoring of monocyte HLA-DR expression for the diagnosis, prognosis, and prediction of sepsis. Frontiers in bioscience (Landmark edition). https://doi.org/10.2741/4547

5. Benlyamani, I., Venet, F., Coudereau, R., Gossez, M., & Monneret, G. (2020). Monocyte HLA-DR Measurement by Flow Cytometry in COVID-19 Patients: An Interim Review. Cytometry. Part A : the journal of the International Society for Analytical Cytology. https://doi.org/10.1002/cyto.a.24249

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

Array NB100-77855R

• HLA-DR Antibodies