# A deep-dive into MHC-related odors: A comment on Schubert et al. (2021)

Sarah Leclaire

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## To cite this version:

Sarah Leclaire. A deep-dive into MHC-related odors: A comment on Schubert et al. (2021). Behavioral Ecology and Sociobiology, 2021, 32 (3), pp.375-376. 10.1093/beheco/arab023. hal-03367860

HAL Id: hal-03367860

https://hal.science/hal-03367860

Submitted on 7 Oct 2021

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# A deep dive into MHC-related odors: a comment on Schubert et al. (2021)

Sarah LECLAIRE¹

¹Laboratoire Évolution & Diversité Biologique (EDB UMR 5174), Université Fédérale de Toulouse
Midi-Pyrénées, CNRS, IRD, UPS. 118 route de Narbonne, Bat 4R1, 31062 Toulouse cedex 9 France

The microbiota is emerging as a fundamental contributor to the metabolic health of the host, and its interplay with the immune system is increasingly being investigated (Zheng et al. 2020). It is therefore not surprising that many behavioral ecologists studying MHC-related odors have recently brought up to date the potential role of microbiota in MHC-related odor production, an hypothesis stated several decades ago (Singh et al. 1990) but rarely tested. The review of Schubert et al. (2021) is therefore very timely.

As mentioned by Shubert et al. (2021), a crucial point to develop credible evidence for microbiota-mediated odor production lies with a better characterization of the odorants that encode MHC characteristics. Many chemically-minded ecologists have focused on the odor fraction retrieved by a single method of gas-chromatography / mass-spectrometry (GCMS). However, the molecules detected by GCMS depend, for instance, on the extraction technique and the GC column used. In addition, standard GCMS methods cannot detect antigen peptides bound by MHC, which have provided, so far, one of the most direct evidence for MHC-related odorants (in mice, fish and humans) (Milinski et al. 2005; Milinski et al. 2013; Sturm et al. 2013). I recommend therefore the concurrent use of different chemical analyze methods, to get a better characterization of the overall odor bouquet of an individual and thus a more extensive view of the potential MHC-related odorants.

Once individual odors have been characterized, statistical methods may be used to determine the specific odorants related to MHC characteristics. However, although such correlative approaches are useful, experimental studies are needed to ascertain the odorants directly related to MHC. Manipulating the MHC is clearly difficult, although recent techniques, such as the modulation of MHC expression (e.g. through epigenetic modification), may be considered. In addition, despite several drawbacks, the use of MHC-congenic lines can also help unravel the odorants related to MHC. These different methods may not be developed on natural animal populations, but experimental studies in captive populations or lab animals, other than mice and rats, might be considered. Such results may prove very informative to inspire investigation in natural contexts. For instance, MHC-congenic lines have been developed in chicken. Investigating the differences in odors between the lines might be of great interest, in particular for behavioral ecologists working on MHC-related odors in birds.

Once potential MHC-related odorants are identified, using either statistical or experimental methods, their behavioral relevance needs to be tested to definitively validate them as mediators of
communication. In vertebrates, odor signals are often complex and many odorants are difficult to isolate or artificially synthesize. The modification of individual odors is thus hard to design, and experimental studies are extremely rare (but see Milinski et al. 2005). This contrasts to other phenotypic traits, such as coloration or ornament size, which are frequently manipulated in behavioral ecology studies. Efforts need thus to be made to come up with inventive methods aiming at modifying odors.

Finally, a good understanding of the chemistry and biosynthetic pathway of the odorants of interest is important to predict their origin (Charpentier et al. 2012). Besides being produced by the microbiota, odorants may originate, for instance, from industrial pollution or from the metabolism, the diet or the eukaryotic pathogens of the host. In several cases, mentioning a microbiota-mediated odor production mechanism may be erroneous. Ecologists should therefore collaborate, for example, with analytical chemists and microbiologists when making predictions about the potential origin of the odorants.

I suggest that putting more effort in characterizing MHC-related odors is key to better predict the potential mechanism of their production. Following those recommendation may also help unraveling the nature and the potential origin of other odor signals, such as sex, individual or group signatures.

## References

* Charpentier MJ, Barthes N, Proffit M, Bessière JM, Grison C (2012) Critical thinking in the chemical ecology of mammalian communication: roadmap for future studies. Funct Ecol 26:769-774

* Milinski M, Croy I, Hummel T, Boehm T (2013) Major histocompatibility complex peptide ligands as olfactory cues in human body odour assessment. Proc R Soc B 280

* Milinski M, Griffiths S, Wegner KM, Reusch TBH, Haas-Assenbaum A, Boehm T (2005) Mate choice decisions of stickleback females predictably modified by MHC peptide ligands. Proc Natl Acad Sci U S A 102:4414-4418

* Singh PB, Herbert J, Roser B, Arnott L, Tucker DK, Brown RE (1990) Rearing rats in a germ-free environment eliminates their odors of individuality. J Chem Ecol 16:1667-1682

* Sturm T, Leinders-Zufall T, Maček B, Walzer M, Jung S, Pömmerl B, Stevanović S, Zufall F, Overath P, Rammensee H-G (2013) Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons. Nature communications 4:1-10

* Zheng D, Liwinski T, Elinav E (2020) Interaction between microbiota and immunity in health and disease. Cell Res 30:492-506