B2M HLA-E Lentivirus

B2M HLA-E Lentivirus are replication incompetent, HIV-based, VSV-G pseudotyped lentiviral particles ready to transduce most mammalian cells, including primary and non-dividing cells. These viruses result in the expression of B2M (beta-2 microglobulin) HLA (human leukocyte antigen)-E driven by an EF1a promoter. The lentiviruses also contain a puromycin selection marker (Figure 1). Figure 1. Schematic of the lenti-vector used to generate B2M HLA-E Lentivirus. HLA-E, or MHC (major histocompatibility complex) class I antigen E, is considered a non-classical MHC class I with low expression and fewer polymorphisms than the remaining HLA. HLA-E is composed of a heavy chain and beta-2 microglobulin (B2M). It binds to specific peptides derived from the classical MHC class I (HLA-A, B, C and G), after these have been processed in the endoplasmic reticulum and the proteosome. The complex of HLA-E with the peptide is recognized by NK cells via the inhibitory receptor CD94/NKG2A/B. Binding to CD94/NKG2C however results in NK cell activation. Expression of HLA-E combined with knockout of HLA-A, B and C, in pluripotent stem cell (PSC) and their differentiated cell types, resulted in these cells escaping attack by CD8+ T cells and NK cytotoxicity. This strategy brings us closer to an almost universal cell donor reality, reducing the risk of immune rejection during cell transplants and alleviating the enormous investment of creating a PSC bank that has representation of all the haplotypes.