Pregnancy is a situation in which genetically diverse cells are situated in apposition with one another without elicitation of an immune response. Fetal evasion of a maternal immune response is believed to be achieved by suppression of classical major histocompatibility complex (MHC) molecule expression together with upregulation of expression of non-classical MHC molecules. One such antigen is human leukocyte antigen (HLA)-G, which is highly expressed in the placenta as both a membrane-bound and a soluble molecule. There are two isoforms of soluble (s) HLA-G, sHLA-G1 and sHLA-G2, which circulate in the peripheral blood during pregnancy and may suppress the immune system of the mother. Here, it is hypothesized that sHLA-G of one or both isoforms has a suppressive effect on subpopulations of peripheral blood leukocytes (T cells, NK cells, and macrophages).
In Aim 1 of this application, using flow cytometry, the specific subpopulations of peripheral blood leukocytes that bind either form of sHLA-G will be identified through the use of fusion proteins of green fluorescent protein and the two isoforms of sHLA-G.
In Aim 2, the cell populations that bind sHLA-G will be isolated and the effects of recombinant sHLA-G1 and sHLA-G2 on each population will be characterized. Elucidation of the consequences of sHLA-G binding to peripheral blood leukocytes is expected to provide meaningful insight into the mechanism of immunomodulation during pregnancy.
