Eutherian Fetoembryonic Defense System (eu-FEDS) Hypothesis - Implications of The Hypothesis

Implications of The Hypothesis

Human sperm and eggs also lack molecules for the immune recognition of "self". These immune markers are also known as major histocompatibility (MHC) antigens or more specifically in humans as human leukocyte antigens (HLA)). Therefore a major question is how are human gametes recognized by immune effector cells. Specifically, their lack of MHC recognition markers should trigger the immune system, resulting in lysis of both sperm and eggs by leukocytes known as natural killer, or NK cells. These cells target and kill other cells lacking such MHC markers, a concept known as "missing self". One distinct possibility is that sperm and eggs are recognized via oligosaccharides expressed on their surfaces. For example, human gametes are coated with carbohydrate sequences that have been implicated in the suppression of NK cell mediated responses.

One of the major corollaries of the eu-FEDS hypothesis is that persistent pathogens and aggressive tumor cells are able to either mimic or acquire the same carbohydrate functional groups used to suppress any immune response that could interfere with the reproductive imperative, thus enabling them to similarly resist the human immune response. These pathogens include HIV-1, helminthic parasites such as schistosomes, and Helicobacter pylori, the bacterium that causes stomach ulcers.

There are some notable examples of this mimicry or acquisition of the same carbohydrate sequences implicated in this protective system by pathogens and aggressive tumor cells. The major carbohydrate sequence linked to glycodelin-A also profusely coats the surface of schistosomes. The profile of the major oligosaccharides linked to CA125 and the major surface glycoprotein of HIV-1 (gp120) almost perfectly overlap. More persistent pathogens linked to the eu-FEDS model may be identified as mass spectrometry methods for sequencing oligosaccharides become more sensitive.