Human Leukocyte antigens

Human Leukocyte antigens

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.

Table 1: Classification of MHC genes
MHC I molecules MHC II molecules
Major Minor Major Minor
HLA-A HLA-E HLA-DP HLA-DM
HLA-B HLA-F HLA-DQ HLA-DO
HLA-C HLA-G HLA-DR

 

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

 

HLA antibodies
Item Clone Pure FITC R-PE CyQ APC PerCP Biotin
Anti-HLA-A+B+C+E TP25.99SF IQP-618P
Anti-HLA-A2 BB7.2 IQP-619R
Anti-HLA-B7 BB7.1 IQP-620P IQP-620R
Anti-HLA-Class I MEM-147 IQP-621P IQP-621R
Anti-HLA-Class I W6/32 IQP-622P IQP-622F IQP-622R IQP-622B
Anti-HLA-DQ1+DQ3 HL-37 IQP-623P
Anti-HLA-DR BRA30 IQP-134P IQP-134F IQP-134R IQP-134C
Anti-HLA-DR MEM-12 IQP-550P IQP-550F IQP-550R IQP-550A IQP-550PC
Anti-HLA-DR L243 IQP-625P IQP-625F IQP-625R IQP-625A
Anti-HLA-DR+DP HL-38 IQP-626P IQP-626F IQP-626R
Anti-HLA-DR+DP HL-40 IQP-627P
Anti-HLA-DR+DP MEM-136 IQP-628P IQP-628F IQP-628R IQP-628A IQP-628B
Anti-HLA-E MEM-E/07 IQP-629P IQP-629B
Anti-HLA-G MEM-G/9 IQP-630P IQP-630F IQP-630R IQP-630A IQP-630B
Anti-HLA-G MEM-G/11 IQP-631P IQP-631F
Anti-HLA-G 5A6G7 IQP-632P IQP-632R IQP-632B
Anti-HLA-G 2A12 IQP-633P IQP-633F
Anti-HLA-G MEM-G/2 IQP-634P
Anti-HLA-G 87G IQP-635P IQP-635F IQP-635R IQP-635B
Anti-HLA-G 01G IQP-636P IQP-636F
Anti-HLA-G 4H84 IQP-637P IQP-637B

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.

 

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