The involvement of HLA-E and -F in pregnancy

Immunobiology of HLA Class-Ib Molecules in Transplantation

“…HLA-Ib is naturally occurring molecules; they are primarily characterized during pregnancy and are considered to play a role in the tolerance of the fetus-the physiological equivalent of a semiallograft [29,30]. The engineering of HLA-Ib tetrameric complexes was used to study their function and potential ligands [31].…”

“…Although HLA-F associates with β2m [48], no information is available on peptide presentation. It is thought to be biologically similar to other HLAIb molecules, such as in pregnancy [29,30] and cancer [32,49]; HLA-F also occurs in circulation as sHLA-F [32] like other sHLA-I molecules. However, the exact function of HLA-F remains to be elucidated.…”

“…This is important from the perspective of viremia (CMV, BK virus) associated with the allograft as part of adaptive immunity. HLA-G expressed on the allograft interacts with ILT2, ILT4 and KIR2DL4 receptors on NK and T cells, leading to the inhibition of cytotoxicity and possibly towards graft acceptance [29,45]. Similarly, HLA-F will interact with ILT2 and ILT4 receptors [29,54] leading to the inhibition of cytotoxicity and graft acceptance; however, it remains to be elucidated whether allograft-associated vascular and endothelial cells, infiltrating leukocytes, can express HLA-F on their surface.…”

“…HLA-G expressed on the allograft interacts with ILT2, ILT4 and KIR2DL4 receptors on NK and T cells, leading to the inhibition of cytotoxicity and possibly towards graft acceptance [29,45]. Similarly, HLA-F will interact with ILT2 and ILT4 receptors [29,54] leading to the inhibition of cytotoxicity and graft acceptance; however, it remains to be elucidated whether allograft-associated vascular and endothelial cells, infiltrating leukocytes, can express HLA-F on their surface. In the case of Bone Marrow Transplantation (BMT) or Hematopoietic Stem Cell Transplantation (HSCT), HLA-F can be expressed on donor immune cells only if they become activated [52].…”

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

“…With a low level of polymorphism its role is thought to be confined to the regulation of NK cell function (Pietra et al, 2009). The HLA-F gene was first identified in 1990 by Geraghty et al (Geraghty et al, 1990;Ishitani et al, 2006). So far it is the nonclassical class I molecule least characterized and neither its native structure nor function is known (Boyle et al, 2006; Goodridge et al, 2010; .…”