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MHC I preparation

Human MHC (HLA): Foundations of Immune Recognition

The Human Major Histocompatibility Complex (MHC), also known as Human Leukocyte Antigen (HLA), plays a pivotal role in the immune system by distinguishing self from non-self molecules. Located on chromosome 6, MHC genes encode proteins that present antigens to T cells, initiating adaptive immune responses. MHC molecules are categorized into three classes—MHC I, MHC II, and MHC III—each with specialized functions in immunity.

Figure 1. Structure of MHC I Molecule

MHC I: Presenting Intracellular Antigens

MHC I molecules are expressed on nearly all nucleated cells and consist of an alpha chain paired with β2-microglobulin (B2M). The alpha chain includes three domains (α1, α2, α3), with α1 and α2 forming a peptide-binding groove that holds peptides (8–10 amino acids) from intracellular sources, such as viral proteins or tumor antigens. These MHC I-peptide complexes are recognized by the T-cell receptor (TCR) on CD8+ cytotoxic T cells, triggering targeted cell destruction. The TCR’s affinity for monomeric MHC I-peptide complexes is low but is significantly enhanced with MHC I tetramers, improving immune detection.

MHC I is essential for antiviral immunity, tumor surveillance, and transplant compatibility. Dysregulation of MHC I presentation can lead to immune evasion in cancers or contribute to autoimmune diseases.

MHC II: Orchestrating Adaptive Immunity

MHC II molecules are primarily found on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells. Composed of α and β chains, the α1 and β1 domains form the peptide-binding groove, which binds extracellular antigens (13–25 amino acids), such as bacterial peptides. MHC II presents these antigens to CD4+ T helper cells, which coordinate immune responses by activating B cells for antibody production and macrophages for pathogen clearance.

MHC II is crucial for immunity against extracellular pathogens and is often implicated in autoimmune diseases like rheumatoid arthritis due to genetic polymorphisms.

MHC III: Supporting Immune Regulation

MHC III genes encode proteins that support immune regulation rather than antigen presentation. These include complement components (C2, C4, factor B), cytokines (e.g., TNF-α), and heat shock proteins. Positioned between MHC I and MHC II regions, MHC III proteins enhance innate immunity, inflammation, and immune signaling, complementing the adaptive roles of MHC I and MHC II.

Variations in MHC III genes are linked to inflammatory disorders, making them a key focus for immune modulation research.

Custom MHC I Complex Services at AtaGenix

AtaGenix offers custom MHC I complex services to support advanced immunological research. Leveraging our eukaryotic expression platform (HEK293), we ensure natural conformations for MHC I complexes, avoiding issues like incorrect folding associated with prokaryotic systems. Our process includes:

Co-expressed Monomers: Biotinylated MHC I heavy chain and β2-microglobulin are co-expressed in HEK293 systems to produce peptide-free monomers.
Peptide Loading: Antigenic peptides are loaded onto MHC I monomers to form stable complexes.
Tetramerization: Monomers are linked with fluorochrome-labeled streptavidin to create tetramers, ideal for T-cell detection.

We validate our MHC complexes using techniques like SPR and FACS to ensure high biological activity, supporting applications in T-cell analysis and drug development.

Applications in Research and Therapeutics

MHC molecules are integral to both research and clinical applications. MHC typing is vital for organ transplantation to reduce rejection risks by matching HLA profiles between donors and recipients. In vaccine development, understanding MHC-peptide interactions enables the design of vaccines that elicit robust T-cell responses, particularly for viral and cancer vaccines. MHC tetramers are widely used to study antigen-specific T-cell populations, advancing immunotherapy research for diseases like cancer and HIV.

Therapeutically, MHC pathways are targets for treating autoimmune diseases, where polymorphisms contribute to disease susceptibility, and cancers, where MHC downregulation enables immune evasion. Custom MHC I complexes are also critical for developing TCR-T cell therapies and TCR-like antibodies, offering new avenues for precision medicine in oncology.

About AtaGenix

AtaGenix is a leading provider of bioreagents for immunological research, offering high-quality products and custom services for MHC-related studies. Our portfolio includes:

High-affinity MHC antibodies
Recombinant MHC proteins with >98% purity
MHC tetramer kits for T-cell analysis
Custom assay development for immune profiling
Custom MHC I complex services

 

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