The human leucocyte antigen (HLA) complex encodes the major histocompatibility complex (MHC) proteins, which are responsible for the regulation of (acceptation in) the immune system. The major histocompatibility complex is divided into two classes, I and II, which in turn are divided in major and minor MHC proteins (see table 1). The expression of the HLA molecules on the surface of cells differentiates self from non-self cells (MHC I)¹ and for that reason play a role in graft rejection. Therefore, matching of HLA proteins (loci) of the donor and the graft reduces the risk of rejection after transplantation. The HLA proteins belonging to the MHC class II present peptides from pathogens to other immune cells and thereby contribute to the immunological response against invading pathogens².

HLA I molecules are inherited from both mother and father. As such, a foetus will express HLA molecules which are different from the maternal HLA proteins. It might be expected that the foetus would be rejected by mother because of this difference. During pregnancy fetal extravillous trophoblasts (EVT) play an important role in embryo implantation and establishment of maternal-fetal immune tolerance. The EVT express MHC class I molecules HLA-C, HLA-E, and HLA-G (but not HLA-A and HLA-B) and avoid immune rejection by maternal leukocytes³. Especially HLA-G has been reported to be important in protecting the fetus from maternal uterine NK cells⁴, promoting vascular adaptations⁵, and providing immune tolerance during pregnancy⁶. In addition, increasing evidence suggests that HLA-G interacts with multiple placental immune cells such as NK cells, macrophages, T cells, and B cells mediated via the inhibitory receptors killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4), and immunoglobulin-like transcript 2 (ITL2) and ITL4⁷.

HLA-G is also present in a soluble form, sHLA-G, in the blood of mother. The presence of sHLA-G is associated with better pregnancy rates⁸. It has been suggested to use sHLA-G to evaluate the quality of embryos after IVF and increase pregnancy rate independent of the morphological score.

To support the use of flow cytometry for studying the complexity of HLA proteins during pregnancy, IQ Products offers various important HLA markers, highlighted in the table below. Are you interested in other markers, different fluorochromes or need help creating a panel for your research purpose? Contact us at techsupport@iqproducts.nl

References

• Parham P, Ohta T (April 1996). “Population biology of antigen presentation by MHC class I molecules”. Science. 272 (5258): 67–74.

• Taylor CJ, Bolton EM, Bradley JA (2011). “Immunological considerations for embryonic and induced pluripotent stem cell banking”. Philosophical Transactions of the Royal Society B. 366 (1575): 2312–2322.

• Apps R, et al. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies. Immunology. 2009;127:26–39. doi: 10.1111/j.1365-2567.2008.03019.x.

• Rouas-Freiss, N., Gonc¸ alves, R.M., Menier, C., Dausset, J., and Carosella, E.D. (1997). Direct evidence to support the role of HLA-G in rotecting the fetus from maternal uterine natural killer cytolysis. Proc. Natl. Acad. Sci. USA 94, 11520–11525.

• Rajagopalan, S. (2014). HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction. Cell Mol. Immunol. 11, 460–466.

• Hunt, J.S., Petroff, M.G., McIntire, R.H., and Ober, C. (2005). HLA-G and immune tolerance in pregnancy. FASEB J. 19, 681–693.

• Ferreira LMR, Meissner TB, Tilburgs T, Strominger JL (2017). HLA-G: At the interface of maternal-fetal tolerance. Trends in Immuno. 38 (4): 272-286

• Rebmann V, Switala M, Eue I, Grosse-Wilde H (May 2010). “Soluble HLA-G is an independent factor for the prediction of pregnancy outcome after ART: a German multi-centre study”. Hum Reprod. 25 (7): 1691–8.