Non-Classical MHC Tetramers

HLA-E, Qa-1b

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 leader_3-11.⁴ However, it is also reported that CD8⁺ T cells can recognize HLA-E loaded with the UL40_15-23 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 leader_3-11-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. 

MR1

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

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. 

TCR

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

References

1.    Miller JD, et al. J Immunol 171: 1369-1375 (2003)
2.    Braud VM, et al. Nature 391: 795-799 (1998)
3.    Lee N, et al. PNAS 95: 5199-5204 (1998)
4.    Tomasec P, et al. Science 287: 1031-1033 (2000)
5.    Heinzel AS, et al. J Exp Med 196: 1473-1481 (2002)
6.    Pietra G, et al. PNAS 100: 10896-10901 (2003)
7.    Salerno-Gonçalves R, et al. J Immunol 173: 5852-5862 (2004)
8.    Derré L, et al. J Immunol 177: 3100-3107 (2006)
9.    Monaco EL, et al. Neoplasia 13: 822-830 (2011)
10.    Weder P, et al. Results in Immunology 2: 88-96 (2012)