The expression of T cell receptors (TCRs) in non-T cells is becoming an intriguing finding that merits further experimentation. The expression of TCRαβ and TCRγδ in cells of the myeloid lineage has been reported in healthy individuals (Puellmann et al., 2006, Legrand et al., 2009, Beham et al., 2011), their decline has been correlated to immune senescence (Fuchs et al., 2012), while increase of expression has been demonstrated in various pathologies including atherosclerosis lesions (Fuchs et al., 2012), tumor microenvironments (Fuchs et al., 2015), lung tuberculosis (Beham et al., 2011), malaria infection (Chorazeczewski et al., 2018, Oakley et al., 2018). Although TCRαβ-positive monocytes and macrophages have been shown to express the necessary for signal transduction molecules ZAP-70, LAT, Fyn and Lck (Beham et al., 2011, Fuchs et al., 2013), literature lacks information as to the assembly and function of the ectopic TCR expression.

Studying the aberrant expression in the monocytes-macrophage-like RAW 264.7 cell line, Antonopoulou et al. (2023) showed the simultaneous presence of TCRαβ and γδ cells, the lack of CD3 but the expression of mainly CD4 molecules, while they could demonstrate that FcγRII/III could compensate the need of CD3 for TCR functioning in these cells.

A non-lymphoid aberrant expression of TCRs has been described by Mytilinaiou et al. (2019), who detected both major histocompatibility complex (MHC) and TCR polymorphic immune molecules in spermatozoa and the female reproductive tract in BALB/c mice, suggesting their involvement in mate selection and spermatozoa guidance towards fertilization. Such hypothesis could provide additional fertility markers, when couples with physiological fertility tests fail to conceive. Focusing on the male counterpart, the present study was designed to delineate and understand the expression of TCRs in sperm.

Spermatogonia differentiate in testicular seminiferous tubules in contact with sertoli cells, which ensure nourishment and protection through the blood-testis-barrier. Following a number of differentiation stages, A4-type spermatogonia undergo either self-renewal, cell death or differentiate into intermediate spermatogonia that are committed to become spermatozoa and divide to produce type B spermatogonia, which will then divide to generate primary spermatocytes (Dym, 1994). After completing the first meiotic division, primary spermatocytes produce secondary spermatocytes, complete the second meiotic division producing haploid spermatids, which after losing the cytoplasmic connections, differentiate into sperm cells in the lumen of the seminiferous tubule, ready to be ejaculated. It is interesting to note that although spermatids that are connected through the cytoplasmic bridges have haploid nuclei, they are functionally diploid, since gene products of one cell may diffuse to neighbor cells (Braun et al., 1989), resulting in differential protein expression within the sperm cell population. Thereafter, sperm cells are guided to the ampulla, enriched with secretions from seminal vesicles and thus the seminal fluid travels through the ejaculatory ducts, passes from the prostate and empties into the urethra.

A number of criteria following basic, extended, advanced and computer-assisted sperm examination have been evoked to evaluate sperm quality (Boitrelle et al., 2021), yet no correlation has been made to protein expression. The hypothesis of MHC/TCR involvement in mate choice is an important feature in reproduction and evolution and needs further exploitation.

Focusing in the contribution of sperm in mate choice, and taking into consideration the observations of TCR expression in semen, the present study was designed to define the expression of TCR and co-receptors and follow the expression during spermatogenesis in testis. Although the results presented herein definitely demonstrate the presence of TCRαβ and γδ even during the early stages of spermatogenesis, supporting thus their involvement in mate choice, the correlation of such expression to natural mating success is still a puzzling issue, therefore preventing the decision to consider the presence of TCR as positive or negative marker to fertility.