HLA-E, HLA-F and HLA-G — The Non-Classical Side of the MHC Cluster

High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and RepressesHLA-EExpression in Human Keratinocytes

“…In addition to regulating NK cells, HLA-E also acts on CD8 + T and natural killer T (NKT) cells to modulate adaptive immune responses 47,48 . HLA-E activates or inhibits NK and CD8 + T cell functions by presenting a narrow range of viral and bacterial antigens 49 . Of note, a viral-derived peptide presented by HLA-E on HIV-1-infected CD4+ T cells activates NK cells and induces cytolysis of virus-infected cells 50 .…”

Dynamic Interaction between Immune Escape Mechanism and HLA-Ib Regulation

“…HLA-E binds CD94/ NKG2A with a higher affinity than CD94/NKG2C [33]. The main peptide source of HLA-E is the leader sequence of HLA-Ia molecules; therefore, the role of HLA-E in innate immunity is to present HLA-E bound to these peptides to NK cells to inhibit NK-mediated lysis through pHLA-E/CD94/NKG2A engagement [7].…”

“…Nevertheless, despite those findings, it is not known yet whether the isoforms of HLA-G1 and HLA-G5 are relevant in vivo under physiological conditions [62]. In terms of peptide presentation, HLA-G differs from other HLA-Ib molecules like HLA-E that presents a very restricted peptide repertoire derived from the signal sequence of other HLA molecules irrespectively of the HLA-E-expressing tissue [7]. In contrast, HLA-G is considered to be a classical peptide presenter like HLA-Ia molecules; however, its peptide repertoire is restricted to the tissue distribution and cell type [7,69,70].…”

“…In terms of peptide presentation, HLA-G differs from other HLA-Ib molecules like HLA-E that presents a very restricted peptide repertoire derived from the signal sequence of other HLA molecules irrespectively of the HLA-E-expressing tissue [7]. In contrast, HLA-G is considered to be a classical peptide presenter like HLA-Ia molecules; however, its peptide repertoire is restricted to the tissue distribution and cell type [7,69,70]. Peptide identification of HLA subtypes is usually performed by affinity purification of the desired HLA molecule from a selected tissue/cell type followed by peptide isolation and mass spectrometric sequencing.…”

“…Contrary to HLA-Ia molecules, they exhibit only a few polymorphisms [5]. HLA-Ib molecules differ not only in their limited polymorphisms from HLA-Ia molecules but also in their restricted peptide repertoire and their distinct tissue distribution [6][7][8]. Typically, the function of classical HLA-Ia molecules is the presentation of peptide antigens to immune effector cells, yet HLA-Ib molecules exhibit a diverse range of functions in innate and adaptive immunity.…”