Sexual Intercourse and Alloimmunity. Influence on Reproduction and Solid Organ Transplantation

Sexual intercourse is associated with recognition of partner-derived major histocompatibility complex (MHC) and minor histocompatibility alloantigens (MiHAs) by females. Male sperm-associated MHC antigens, expressed on spermatozoa and leukocytes, as well as MiHAs including sperm-specific antigens (SPAGs), are recognized by female T lymphocytes infiltrating the cervicovaginal region. This can occur via direct presentation of male MHC molecules on male antigen presenting cells and indirect presentation of male antigen peptides (MHC and MiHAs) bound to female MHC molecules on female antigen presenting cells. This process along with the presence of anti-inflammatory chemokines and cytokines and sHLA-G present in seminal fluid leads to activation of male antigen-specific FOXP3+ Treg locally and in regional lymph nodes. This regulatory response has been shown to promote survival and progression of spermatozoa within the cervical mucus as well as implantation of the embryo. Most important, it is believed to set the stage for fetal-maternal tolerance during pregnancy. Conversely, under certain circumstances, alloresponses to male antigens can lead to the production of anti-MHC and anti-sperm-specific antigens antibodies resulting in infertility. Altogether, these observations show that alloimmunity induced after sexual intercourse plays an essential role in reproduction. In addition, while the influence of pregnancy in transplantation is well established, some studies suggest that repeated sexual exposure to male antigens can increase the risk of solid organ transplant rejection.