"HLA-C: evolution, epigenetics, and pathological implications in the major histocompatibility complex".

Front Genet

Escuela Superior Politécnica del Litoral, Laboratorio para investigaciones biomédicas, Facultad de Ciencias de la Vida (FCV), Guayaquil, Ecuador.

Published: July 2023


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

HLA-C, a gene located within the major histocompatibility complex, has emerged as a prominent target in biomedical research due to its involvement in various diseases, including cancer and autoimmune disorders; even though its recent addition to the MHC, the interaction between HLA-C and KIR is crucial for immune responses, particularly in viral infections. This review provides an overview of the structure, origin, function, and pathological implications of HLA-C in the major histocompatibility complex. In the last decade, we systematically reviewed original publications from Pubmed, ScienceDirect, Scopus, and Google Scholar. Our findings reveal that genetic variations in HLA-C can determine susceptibility or resistance to certain diseases. However, the first four exons of HLA-C are particularly susceptible to epigenetic modifications, which can lead to gene silencing and alterations in immune function. These alterations can manifest in diseases such as alopecia areata and psoriasis and can also impact susceptibility to cancer and the effectiveness of cancer treatments. By comprehending the intricate interplay between genetic and epigenetic factors that regulate HLA-C expression, researchers may develop novel strategies for preventing and treating diseases associated with HLA-C dysregulation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350511PMC
http://dx.doi.org/10.3389/fgene.2023.1206034DOI Listing

Publication Analysis

Top Keywords

major histocompatibility
12
pathological implications
8
histocompatibility complex
8
hla-c
7
"hla-c evolution
4
evolution epigenetics
4
epigenetics pathological
4
implications major
4
histocompatibility complex"
4
complex" hla-c
4

Similar Publications

Characterization of the extrinsic and intrinsic signatures and therapeutic vulnerability of small cell lung cancers.

Signal Transduct Target Ther

September 2025

State Key Laboratory of Molecular Oncology & Department of Medical Oncology & Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor strongly associated with exposure to tobacco carcinogens, is characterized by early dissemination and dismal prognosis with a five-year overall survival of less than 7%. High-frequency gain-of-function mutations in oncogenes are rarely reported, and intratumor heterogeneity (ITH) remains to be determined in SCLC. Here, via multiomics analyses of 314 SCLCs, we found that the ASCL1/MKI67 and ASCL1/CRIP2 clusters accounted for 74.

View Article and Find Full Text PDF

Natural killer (NK) cell licensing is an educational process that enhances responsiveness to activating signals in maturing NK cells and is predominantly regulated by major histocompatibility complex (MHC) class I-specific inhibitory signals. However, the role of non-MHC signalling in this process remains unclear. Here, we investigated the role of FcRγ, an adaptor protein associated with activating receptors, in the regulation of NK cell responsiveness.

View Article and Find Full Text PDF

Role of Splenocytes on T Cells and Its Cytokine Network in Rheumatoid Arthritis.

Crit Rev Immunol

September 2025

Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala, India 695581.

Rheumatoid arthritis (RA) is a chronic autoimmune condition that impacts the immune system, especially through changes in the splenic immune cell system. This review provides an overview of the role of splenocytes in T cell signaling and their immune response in RA patients. The spleen acts as a critical site for the activation and differentiation of splenic immune cells like T cells, B cells, macrophages, dendritic cells, and NK cells.

View Article and Find Full Text PDF

Invasive ductal carcinoma (IDC) is a major type of breast cancer. The utilization of inhibitors targeting histone methyltransferases introduces novel therapeutic avenues for the treatment of cancer. Immunohistochemistry, Western blot, and reverse transcription quantitative polymerase chain reaction experiments were applied to assess the levels of EHMT2 in IDC and adjacent tissues.

View Article and Find Full Text PDF

Multiplex engineering using microRNA-mediated gene silencing in CAR T cells.

Front Immunol

September 2025

Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Background: Multiplex gene-edited chimeric antigen receptor (CAR) T-cell therapies face significant challenges, including potential oncogenic risks associated with double-strand DNA breaks. Targeted microRNAs (miRNAs) may provide a safer, functional, and tunable alternative for gene silencing without the need for DNA editing.

Methods: As a proof of concept for multiplex gene silencing, we employed an optimized miRNA backbone and gene architecture to silence T-cell receptor (TCR) and major histocompatibility complex class I (MHC-I) in mesothelin-directed CAR (M5CAR) T cells.

View Article and Find Full Text PDF