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Background of Human Leukocyte Antigen

Human leukocyte antigen (HLA) is the major histocompatibility complex encoded by the HLA gene complex. The gene segment it is located in is also the gene with the highest gene density and the most polymorphisms among human chromosomal regain that we know of. HLAs can be classified into three categories according to their function and structure, and are further subdivided into more than a dozen subgroups. For each person, the HLA protein has a unique structure, and the immune system distinguishes self-cells from non-self-cells based on this structural difference, which leads to an attack against the invaders, so the difference in HLA among people is often the leading cause of organ transplant rejection.

Structure Prediction of HLA class I histocompatibility antigen, alpha chain F.Fig.1 Structure Prediction of HLA class I histocompatibility antigen, alpha chain F. (Uniprot ID P30511; obtained from Alphafold)

Functions and Mechanisms of Human Leukocyte Antigen

When a cell is infected with a virus, class I HLA presents viral fragments from the interior of the cell to killer T cells and binds to KIR molecules on their surface, allowing the cell to be destroyed by the immune system. In contrast, class II HLAs present extracellular antigens to CD4-positive T lymphocytes, which in turn promote B cell expansion, thereby activating the immune response.

Applications and Pathology of HLA Cell Lines

HLA is closely related to the body's immune response, regulation, and monitoring, and is of great significance in the study of autoimmune diseases, tumor immunity, organ transplantation, and reproductive immunity. Overexpression of HLA genes or HLA protein disorder and misfolding can lead to various autoimmune diseases. HLA is the bridge connecting immunology and clinical disease treatment. With the development of research methods and technologies, more discoveries and broader prospects will be made.

Published Data

Paper Title HLA-E and HLA-F are overexpressed in glioblastoma and HLA-E increased after exposure to ionizing radiation
Journal Cancer Genomics & Proteomics
Published 2022
Abstract Although the central nervous system has been considered an immunoprivileged site with enhanced immune responses, Glioblastoma (GBM) appears to benefit from this immunosuppressive environment. The nonclassical HLA class Ib molecules, HLA-E, HLA-F, and HLA-G, have been previously described as being involved in the protection of semi-allogeneic fetal allografts from maternal immune responses, graft tolerance as well as tumor immune escape. Unfortunately, their role in GBM remains poorly understood. Therefore, investigators aimed to characterize the relationship between the transcriptional expression of these molecules in GBM, the clinicopathological and molecular features of GBM, and the effects of ionizing radiation. They analyzed HLA-E, HLA-F, and HLA-G mRNA expression in 69 GBM tissue samples and 21 non-tumor brain tissue samples (controls) by reverse transcription PCR. In addition, two primary GBM cell cultures were stimulated with ionizing radiation to determine the effect of ionizing radiation on the expression of nonclassical HLA molecules. The results showed that both HLA-E and HLA-F were significantly upregulated in GBM samples, and ionizing radiation increased the HLA-E expression in GBM cells in vitro. HLA-E and HLA-F play important roles in GBM biology and can be used as diagnostic biomarkers, HLA-E can also act as a prognostic biomarker.
Result The experimental results showed that both HLA-E and HLA-F were significantly upregulated in GBM samples. Subsequent survival analysis revealed a significant association between low expression of HLA-E and shorter survival in GBM patients. Dysregulated expression of these two molecules was also observed between patients with methylated and unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoters. Based on this result, the researchers speculated that tumor cells expressing HLA-E may be selectively close to the host and related to the good response shown in subsequent treatment modalities. In conclusion, researchers demonstrate the clinical diagnostic potential of HLA-E and HLA-F as biomarkers, but the roles of HLA-E and HLA-F molecules in the antitumor response and development of GBM still need to be further explored.

Survival analysis of HLA-E and HLA-F expression in GBM patients performed by Gehan-Breslow-Wilcoxon test.Fig.2 Survival analysis of HLA-E and HLA-F expression in GBM patients performed by Gehan-Breslow-Wilcoxon test. (Hrbac, 2022)

Reference

  1. Hrbac, T.; et al. HLA-E and HLA-F are overexpressed in glioblastoma and HLA-E increased after exposure to ionizing radiation. Cancer Genomics & Proteomics. 2022, 19: 151-162.

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