https://www2.psy.uq.edu.au/~uqbziets/Havlicek2009%20MHC%20correlated%20mate%20choice.pdf

MHC-correlated mate choice in humans: A review

This prospective study aimed to evaluate the changes in olfactory sensitivity of oral contraceptive (OC) (pill) users among 60 women who underwent rhinomanometric and olfactometric determinations during the follicular periovular and luteal phases of the menstrual cycle and at day 7 14 and 21 of contraceptive intake. 31 women used 30 mcg ethinyl estradiol plus 75 mcg gestodene and 29 women used 20 mcg ethinyl estradiol plus 150 mcg desogestrel. Rhinomanometry showed higher but not statistically significant values during the periovular phase than in the follicular and luteal phases. Olfactometry showed a higher sensitivity during the follicular and periovular phases than during the luteal phase of the menstrual cycle. The rhinomanometric surveys in pill users were statistically different from those of the luteal phase (P < 0.02) and the follicular and periovular phases (P < 0.001). The olfactometric thresholds during the period of contraceptive use were statistically different from those of the follicular phase for a few odorous substances and from those of the periovular phase for each odorous substance but similar to those of the luteal phase (P = NS). In conclusion unlike the rhinomanometric airflow and transnasal pressure the olfactory threshold to odours seems to depend on the variations of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of OCs. (authors)

/pdf/a-prospective-study-evidencing-rhinomanometric-and-2bl58jpqgr.pdf

A prospective study evidencing rhinomanometric and olfactometric outcomes in women taking oral contraceptives

http://mateolab.uchicago.edu/mateo_indiv_rec.pdf

The nature and representation of individual recognition odours in Belding's ground squirrels

Mice prefer to mate with individuals expressing different MHC genes from their own. Volatile components presenting MHC-dependent odor types are present in urine and can be detected by mice, as shown by extensive behavioral studies. Similar odor types are suspected to influence human behavior as well. Although a recent report indicates that MHC expression influences the ratio of volatile compounds such as phenylacetic acid, so far no other means than studying the behavior of mice or rats has been available to assess odor types. Here, we report the ability of a gas sensor array (referred to as “electronic nose”) to detect MHC-dependent odor types. The electronic nose consists of an array of chemophysical detectors, in our case quartz crystal microbalances and semiconducting metal-oxide sensors that change frequency or conductivity upon binding of very small numbers of individual molecules present in the gas phase of odorous fluids. The pattern of changes is characteristic for a particular smell. Our electronic nose distinguishes the urine odor types of MHC congenic mouse strains, MHC class I mutant mice, and HLA-A2 transgenic mice. In addition, MHC-dependent odor types can be detected in serum. The device also clearly differentiates between individual odor types of human sera from HLA homozygous individuals; however, HLA expression seems to have only a secondary influence. Thus, odor-type research can now be carried out with an objective and fast through-put system independent of behavioral studies.

https://www.pnas.org/content/pnas/98/16/9249.full.pdf

“Electronic nose” detects major histocompatibility complex-dependent prerenal and postrenal odor components

Natural selection has favored the evolution of behaviors that benefit not only one's genes, but also their copies in genetically related individuals. These behaviors include optimal outbreeding (choosing a mate that is neither too closely related, nor too distant), nepotism (helping kin), and spite (hurting non-kin at a personal cost), and all require some form of kin detection or kin recognition. Yet, kinship cannot be assessed directly; human kin detection relies on heuristic cues that take into account individuals' context (whether they were reared by our mother, or grew up in our home, or were given birth by our spouse), appearance (whether they smell or look like us), and ability to arouse certain feelings (whether we feel emotionally close to them). The uncertainties of kin detection, along with its dependence on social information, create ample opportunities for the evolution of deception and self-deception. For example, babies carry no unequivocal stamp of their biological father, but across cultures they are passionately claimed to resemble their mother's spouse; to the same effect, 'neutral' observers are greatly influenced by belief in relatedness when judging resemblance between strangers. Still, paternity uncertainty profoundly shapes human relationships, reducing not only the investment contributed by paternal versus maternal kin, but also prosocial behavior between individuals who are related through one or more males rather than females alone. Because of its relevance to racial discrimination and political preferences, the evolutionary pressure to prefer kin to non-kin has a manifold influence on society at large.

Human kin detection

The major histocompatibility complex (MHC) has been linked to encoding for individual olfactory identity. Experiments in mice and rats proved that behavior and mating were, at least in part, determined by genes within the MHC. This study was aimed at investigating whether sHLA are excreted in human urine, saliva and sweat. In particular examination of the molecular forms in these fluids would give clues to whether break down forms of soluble MHC molecules might participate in shaping behavior. Major bands of 45, 40, and 23 kD were detectable. Increased levels of sHLA were measured using a quantitative ELISA in urine shortly before ovulation decreasing to normal levels thereafter. In animal models strain specific MHC‐linked odor cues have been detected in urine. Thus, excretion of sHLA in urine might indicate a similar role for these molecules in humans.

Molecular forms of soluble HLA in body fluids: potential determants of body odor cues

Background. In vitro, soluble MHC (sMHC) antigens modulate and induce apoptosis in alloreactive and antigen-specific T cells, demonstrating their potency to regulate T cell-mediated immune responses. However, their efficacy to regulate immunological responses in vivo remains unclear. Here, we report that repetitive intraperitoneal injection of recombinant Lewis rat-derived MHC class I antigens in Dark Agouti (DA) rats modulates alloreactivity. Methods. RT1.Al (Lewis derived) genes were cloned into mammalian expression vectors, and RT1.Aa (DA derived) genes were used to transfect a rat myeloma cell line. RT1.Al molecules were injected intraperitoneally in DA recipients that subsequently underwent transplantation with Lewis-derived cardiac allografts. Results. Soluble class I antigens were secreted by the transfected cells and were shown to be heterodimeric, peptide-loaded, and conformationally folded. Injection of donor-derived soluble MHC significantly reduced the ability of recipient animals to mount a cytotoxic T-cell response to donor-derived tissue. More interestingly, this treatment significantly prolonged donor-graft survival and allowed 60% of treated animals to develop graft tolerance (>120 days), when donor sMHC were combined with a single subtherapeutic dosage of cyclosporine. Thymectomy of recipient animals before transplantation did not interfere with induction of peripheral tolerance. Conclusions. Donor-derived sMHC are potential tolerogens for down-regulating the cytotoxic T-cell response of animals that undergo transplantation. Thus, these data provide for the first time a rationale for the application of directly injected sMHC in vivo to down-regulate immunological responses and aid the induction of graft tolerance.

Donor-derived soluble MHC antigens plus low-dose cyclosporine induce transplantation unresponsiveness independent of the thymus by down-regulating T cell-mediated alloresponses in a rat transplantation model.

Soluble, recombinant MHC class I molecules induce indefinite graft survival

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Molecular forms of soluble HLA in body fluids: potential determants of body odor cues

Donor-derived soluble MHC antigens plus low-dose cyclosporine induce transplantation unresponsiveness independent of the thymus by down-regulating T cell-mediated alloresponses in a rat transplantation model.

Soluble, recombinant MHC class I molecules induce indefinite graft survival

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