Non-classical MHC: 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.
MHC class I-related protein (MR1) is classified as a non-classical class I molecule and has the ability to activate mucosal-associated invariant T cells (MAIT cells) by presenting vitamin B metabolites to them. Similar to MHC class I molecules, MR1 associates with β2-microglobulin (β2m), and like CD1, MR1 is a monomorphic molecule. While MHC class I molecules bind to peptides and CD1d binds to glycolipids, MR1 presents microbial vitamin B metabolites to MAIT cells. In addition, some other drugs and drug-like molecules are reports to be presented by MR1.
Human MAIT cells are abundant and localize in the mucosa, liver, and peripheral blood. MAIT cells are proposed to act as innate T cells and primarily respond to bacterial and mycotic infections. They are also reported to be associated with autoimmune diseases.
Human MR1 Tetramer is a reagent prepared by tetramerizing biotinylated human MR1/ β2m complexes with phycobiliprotein-labeled streptavidin.
Human MR1 Tetramer recognizes human MAIT cells the bind to specifically to the MR1/MR1-ligand complex.
For Research Use Only. Not for use in diagnostic procedures.
- 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)