Creative BioMart offers MHC I and MHC II multimer customization services designed to support T cell functional testing in T cell related research. Recognition of peptide MHC class I and II molecules by T cells plays a very important role in the control of intracellular pathogens and cancer cells through effective T cell stimulation. These interactions play an important role in immune dysregulation such as autoimmune diseases. Labeling of antigen-specific T cells with peptide-MHC multimers provides an invaluable method for monitoring T cell-mediated immune responses.

pMHC Multimers

Peptide-MHC (pMHC) multimers have become the "gold standard" for the detection and isolation of antigen-specific T cells. Traditional T cells coordinate immune responses to pathogens by recognizing foreign protein antigens in the form of peptides presented on the cell surface bound to MHC molecules. The key to identification is the heterodimeric αβ T-cell receptor (αβTCR), which cooperates with the CD4 or CD8 coreceptor to bind pMHC to generate an intracellular transduction cascade leading to T-cell activation. This way of directly labeling antigen-specific T cells is of great value, while tetramers have also been used to quantify the relative dissociation rates (bulk or single-cell level) of TCR binding. In recent years, MHC tetramers have been used to label most αβ T cells and γδ T cells, especially for flow cytometry analysis and in situ staining. For example for CD8+ T cells, the use of tetramers of MHC class I molecules deficient in CD8 binding can more accurately measure the off-rate of TCR binding. Similarly, tetramers can be physically purified from antigen-specific T cells by flow cytometry. Currently, the more widely used multimeric forms of exoMHC include dimers, tetramers, pentamers, lipid vesicles and dextromers. All of these formats contain multiple peptide-MHC complexes or other T cell ligands that form multiple bonds with the TCR for stable binding for labeling and purification of specific specificity T cells.

Fig.1 Evolution of MHC multimers. (Jun Chang et al., 2021)

MHC Mutlimers Service

The recombinant protein expression experimental team of Creative BioMart has rich experience in manufacturing. We provide a variety of expression system options to meet your individual needs as much as possible. Customers can choose custom pMHC monomers according to project needs, and we provide a variety of expression systems for protein production. We will then assemble the produced monomers into dimers, tetramers, pentamers or dextromers according to your needs. In addition, we also offer the generation of some fluorescently tagged multimeric proteins, which can be used for in situ detection. Fluorescent label-based bleed sorting enables the quantification and isolation of antigen-specific T cells in biological samples such as blood, cultured cell lines, lymphatic fluid, synovial fluid, and more. Likewise, it can perform immunohistochemistry (IHC) on solid tumor samples. If there are other tags of interest or tags that are suitable for your analysis method, you can communicate with our experts.

Advantages of MHC Mutlimers

Applications of MHC multimer technology encompass functions such as quantification and analysis of antigen-specific T cells, cell sorting, depletion, stimulation to replace antigen-presenting cells, and single-cell sorting by DNA barcoding. MHC multimer technology complements the affinity of T cell receptor-MHC/peptide complexes through multivalent interactions, although this affinity is relatively low compared to antigen-antibody affinity. High-quality MHC multimers will help researchers conduct research easily, and our knowledge will help you accelerate target discovery and therapeutic development.

Fig.2 The advantage of peptide–MHC tetramers and other multimers for the detection of antigen-specific T cells. (Davis M M et al., 2011)

Creative BioMart has an experienced immunology team whose knowledge will help your research and development move forward as quickly as possible. Our protein production platforms have proven mechanisms to enable shorter lead times. Please contact us if you are interested.

References

• Chang, Jun. MHC multimer: A Molecular Toolbox for Immunologists[J]. Molecules and Cells 44.5 (2021): 328.
• Davis M M, Altman J D, Newell E W. Interrogating the repertoire: broadening the scope of peptide–MHC multimer analysis[J]. Nature Reviews Immunology, 2011, 11(8): 551-558.