HLA-C Human
Description
Immune Regulation
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Adaptive Immunity: Presents viral/cancer peptides to cytotoxic CD8+ T cells .
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Innate Immunity: Binds inhibitory/activating KIRs on NK cells, modulating cytotoxicity . High HLA-C expression enhances NK-mediated antiviral responses but risks autoimmunity .
Pregnancy and Maternal-Fetal Tolerance
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Extravillous trophoblasts (EVTs) uniquely express HLA-C (not HLA-A/B), which interacts with decidual NK cells to balance immune tolerance and pathogen defense . NLRP2 and NLRP12 proteins fine-tune HLA-C levels on EVTs to prevent excessive inflammation .
Infectious Diseases
Autoimmune and Inflammatory Disorders
Transplantation
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High HLA-C expression in donors increases graft-versus-host disease risk post-hematopoietic stem cell transplantation .
Genetic and Epigenetic Regulation
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A SNP 35 kb upstream of HLA-C (rs9264942) modulates expression via miRNA binding (e.g., miR-148a), with the C allele linked to lower expression and higher HIV susceptibility .
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Exons 1–4 are hotspots for epigenetic silencing (e.g., hypermethylation in alopecia areata), reducing immune activation .
Allele-Specific Expression
| Allele | Surface Expression | Clinical Impact |
|---|---|---|
| HLA-C05* | High | Protective in HIV, risky in Crohn’s |
| HLA-C07* | Low | Linked to COPD and HPV+ cancers |
Transfection studies in 721.221 cells confirmed C05* expresses ~2-fold higher than C07*, mirroring in vivo lymphocyte data .
Evolutionary Insights
HLA-C originated ~10 million years ago via HLA-B duplication, evolving distinct KIR-binding properties . Its lower polymorphism compared to HLA-A/B suggests recent selective pressures balancing immune defense and self-tolerance .
Clinical and Research Implications
Product Specs
Product Science Overview
The Major Histocompatibility Complex (MHC) is a set of cell surface proteins essential for the acquired immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility. MHC molecules are divided into two primary classes: MHC class I and MHC class II. This article focuses on MHC class I, specifically the HLA-C molecule, and its recombinant form.
MHC class I molecules are heterodimers composed of a heavy chain (α chain) and a light chain (β2-microglobulin). The heavy chain is encoded by the HLA (Human Leukocyte Antigen) genes, which include HLA-A, HLA-B, and HLA-C . The primary function of MHC class I molecules is to present peptide fragments derived from intracellular proteins to cytotoxic T cells (CTLs). This presentation is crucial for the immune system to detect and eliminate infected or malignant cells .
HLA-C is one of the three classical MHC class I molecules in humans. It is less polymorphic compared to HLA-A and HLA-B but plays a significant role in immune response. HLA-C molecules are expressed on the surface of almost all nucleated cells and present endogenous peptides to CTLs . The interaction between HLA-C and CTLs is vital for the immune system’s ability to target and destroy cells that are infected with viruses or have become cancerous .
Recombinant HLA-C refers to the HLA-C molecule that has been produced using recombinant DNA technology. This involves inserting the gene encoding HLA-C into a suitable expression system, such as bacteria or mammalian cells, to produce the protein in vitro. Recombinant HLA-C is used in various research applications, including studying the immune response, developing vaccines, and designing immunotherapies .
- Immunotherapy: Recombinant HLA-C is used to develop therapies that can enhance the immune system’s ability to fight cancer and infectious diseases. By understanding how HLA-C presents peptides to CTLs, researchers can design strategies to boost the immune response against tumors and pathogens .
- Vaccine Development: Studying the interaction between HLA-C and CTLs helps in the design of vaccines that can elicit strong cellular immune responses. This is particularly important for vaccines against viruses that evade the immune system by hiding within host cells .
- Transplantation: HLA-C typing is crucial in organ transplantation to ensure compatibility between donors and recipients. Recombinant HLA-C can be used to develop assays for precise HLA typing, reducing the risk of transplant rejection .
