Schlüsselwort: carcinoembryonales Antigen

"The analysis of the carcinoembryonic antigen and pregnancy specific glycoprotein gene family of the horse" A well-regulated immune reaction is built upon the coordination of the single cells from the innate and the acquired immune system. Next to secreted molecules like cytokines and chemokines such a reaction is mainly mediated by surface molecules belonging to different receptor families found within the leucocyte receptor complex. Beside the well-known and analyzed families like the KIR- or the LIR-family, the CEA gene family belongs to them. This family is embedded within the extended region of the leucocyte receptor complex and is characterized for different mammalian species in a more or less large amount. In the genome of the horse clues for the existence of members belonging to the CEA gene family could be found and their availability was later experimentally proven. While the extension of this family is well examined in other species, like the human and in rodent species, for example mouse and rat, for horses such things are relatively unknown. Based on genome analyzations, partly confirmed during a bachelor thesis (Aleksic, 2010), it could be assumed that in the horse the expression of this family contain quite a few members, among which also secreted members are. Such secreted members are also known from other species developing a haemochorial placenta, in most cases the location where they are expressed, and are referred to as PSGs. In distinction to them the horse is building an epitheliochorial placentation in which the fetomaternal contact is marginally, except for the region of the endometrial cups, where a situation quite similar to this of the haemochorial placenta could be found. This specific members were already well characterized by the group of Robert Kammerer (Aleksic et al, 2016). There was a special eyemark on the membrane-anchored members of this family during the here presented research. Another characteristic of this CEA gene family is the expression of signaling motives by an ITIM or ITAM localized in their cytoplasmatic tail. Hints for the development of such kind of motives are also apparent in the equine CEA gene family. The expression for two of the ITIM-receptor bearing members of the horse, CEACAM1 and CEACAM43 is already proven whereas the detected splice variations are yet known from the mouse. The remaining members meant to bear an ITIM or ITAM in their cytoplasmatic part, seemed to have lost this signaling motives. After sequence analyzing of this members in neither of this expressed versions of the CEACAMs a signaling motive could be detected. Therefor some extraordinary motives like a special repetitive sequence could be characterized as an extracellular part of the CEACAM54, still present in the sequence of the finally expressed gene. Expression studies over a generation of a fusion protein de facto expression of this gene could be confirmed. The only ITAM bearing member of the CEA genes in the horse, the CEACAM41, lost this motive based on the results here. In all of the here detected splice variations the loss of the transmembrane domain suggest a secreted molecule. In other characterized species, like the dog, where ITAM-bearing CEACAMs can be detected, this signaling motives are preserved and in difference to the horse rather duplicated. Diverse from other species the expression pattern from the secreted PSG-like CEACAMs of the horse is not limited to the placental tissue but instead an increased expression upon the immunological cells and especially on the t-lymphocyte subpopulation was detected. The immunological importance of this secreted equine CEACAMs is underlined by the fact, that some members, like the CEACAM55, which is exclusively expressed upon CD4-positive T-cell, are only expressed on a particular subpopulation of the lymphocytes. Within the subpopulation of the t-cells helper cells can be located, which mediate a well-regulated immune reaction. Outlook Lymphocytes and especially some of their subsets like the CD4-positive T-helper cells are mediating a regulated immune response. The here identified population of secreted PSG in the horse like CEACAMs in this part of the activated lymphocytes could play a pivotal role in this regulation mechanism. Because in contrast to the cytokines and chemokines they are much more stable and can facilitate immunological communication between cells over a long distance in the body. Upon this thought the here presented work is the basis for further research on this field. In other species hemophilic and heterophilic interactions between members of the CEA gene family were shown. Such an interaction as well as correlations and interactions of the different members of the CEACAMs have not been proven for horses so far and need to be done.