Non-Classical MHC Tetramers
MBL International offers tetramers for the following non-classical MHC targets: HLA-E, Qa-1b, and MR1. Human leukocyte antigen E (HLA-E) is a non-classical class I molecule recognized by natural killer (NK) cells and CD8+ T cells. HLA-E is expressed in almost all tissues including lung, liver, skin and placental cells.3 HLA-E expression is also detected in solid tumors (e.g., osteosarcoma and melanoma).9 HLA-E binds to TCR expressed on CD8+ T cells, resulting in the T cell activation.6 HLA-E is also known to bind CD94/NKG2 receptor expressed on NK cells and CD8+ T cells.2 CD94 can pair with several different isoforms of NKG2 to form receptors with potential to either inhibit (NKG2A, NKG2B) or promote (NKG2C) cellular activation.
HLA-E preferably binds to a peptide derived from amino acid residues 3-11 of the leader sequences of most HLA-A, -B, -C, and -G molecules, but cannot bind its own leader peptide.2 Under physiological conditions, the engagement of CD94/NKG2A with HLA-E, loaded with peptides from the HLA class I leader sequences, usually induces inhibitory signals. Cytomegalovirus (CMV) utilizes the mechanism for escape from NK cell immune surveillance via expression of the UL40 glycoprotein, mimicking the HLA-A leader3-11.4 However, it is also reported that CD8+ T cells can recognize HLA-E loaded with the UL4015-23 peptide derived from CMV Toledo strain and play a role in defense against CMV.6 A number of studies revealed several important functions of HLA-E in infectious disease and cancer.5,7,8
The HLA-E tetramer is comprised of human class I HLA-E*01:03 and epitope peptide derived from the HLA-A leader, and it can detect HLA-E*01:03-restricted HLA-A leader3-11-specific NK cells and CD8+ T cells by flow cytometry.
The non-classical class I mouse homolog of HLA-E tetramer, Qa-1b tetramer, is now available.
The MHC class I-related protein MR1 is a membrane protein non-covalently bound to β2-microglobulin (β2m), which is known as one of the non-classical MHC class I molecules. It is expressed in almost all cell types of the body. Under steady-state conditions, it is not present on the cell surface, but localized in the endoplasmic reticulum. Upon stimulation, for example, during an infection, MR1 molecules associated with microbial vitamin B metabolites migrate to the cell surface to present them to and thereby activate MAIT cells.
Common ligands for MR1
CD1d is a membrane protein non-covalently bonded to β2-microglobulin (β2m) and shows high homology between human and mouse. CD1d can present α-galactosylceramide (α-GalCer), a glycolipid extracted and isolated from the marine sponge, and this complex can activate human and murine CD1d-restricted NKT cells.
A TCR Tetramer is a reagent prepared by tetramerizing biotinylated antigen-specific TCRs with the help of phycobiliprotein-labeled streptavidin. MBL has efficiently manufactured a TCR Tetramer reagent, which is recognized by MHC, and has successfully commercialized it. These products have been used to monitor T cell immune responses in research studies and clinical trials.
For Research Use Only. Not for use in diagnostic procedures.
Learn more about the other types of MHC Molecules
- Miller JD, et al. J Immunol 171: 1369-1375 (2003)
- Braud VM, et al. Nature 391: 795-799 (1998)
- Lee N, et al. PNAS 95: 5199-5204 (1998)
- Tomasec P, et al. Science 287: 1031-1033 (2000)
- Heinzel AS, et al. J Exp Med 196: 1473-1481 (2002)
- Pietra G, et al. PNAS 100: 10896-10901 (2003)
- Salerno-Gonçalves R, et al. J Immunol 173: 5852-5862 (2004)
- Derré L, et al. J Immunol 177: 3100-3107 (2006)
- Monaco EL, et al. Neoplasia 13: 822-830 (2011)
- Weder P, et al. Results in Immunology 2: 88-96 (2012)