J. Kromer, T. Hummel, D. Pietrowski, A. S. Giani, J. Sauter, G. Ehninger, A. H. Schmidt, I. Croy

Attraction is a miracle to most of us and only some of the many factors mediating mate choice involve odours. However, within the world of human olfaction, there seems to be no perfect mate but a perfect partner and this depends on HLA match.

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    Influence of HLA on human partnership and sexual satisfaction

    by J. Kromer, T. Hummel, D. Pietrowski, A. S. Giani, J. Sauter, G. Ehninger, A. H. Schmidt, and I. Croy



    The major histocompatibility complex (MHC, called HLA in humans) is an important genetic component of the immune system. Fish, birds and mammals prefer mates with different genetic MHC code compared to their own, which they determine using olfactory cues. This preference increases the chances of high MHC variety in the offspring, leading to enhanced resilience against a variety of pathogens. Humans are also able to discriminate HLA related olfactory stimuli, however, it is debated whether this mechanism is of behavioural relevance. We show on a large sample (N = 508), with high-resolution typing of HLA class I/II, that HLA dissimilarity correlates with partnership, sexuality and enhances the desire to procreate. We conclude that HLA mediates mate behaviour in humans.

    Body odours can create immediate sexual attraction. Both, men and women of various cultures seek out perfumes which highlight their body odour in the most desirable way. The famous novel “Perfume” by Patrick Suskind describes a perfume made of body odours that drives people into ecstasy and makes them forget civilized behaviour. However, recent research indicates that the ‘olfactory match’ between people, rather than a universally irresistible smell might be the key to olfactory attraction. We investigated the relation of HLA dissimilarity, which is perceived through the olfactory chemosignaling, with human mate choice.

    In animals, immunologic compatibility determines individual variation of mate choice and is partly conveyed by olfactory cues. The individual genetic major histocompatibility complex (MHC) represents a part of the adaptive immune system. MHC molecules are located on the surface of cells and play a key role in discriminating between endogenous and exogenous, potentially pathogenic material. Genes of the MHC gene cluster are expressed in a co-dominant way. When given a choice, mice and sticklebacks prefer mates with dissimilar MHC molecules compared to their own. This is advantageous from an evolutionary point of view: The co-dominant expression increases the chances of high MHC variety in the offspring of MHC dissimilar compared to MHC similar couples, which in turn leads to enhanced resilience amongst a variety of pathogens.

    MHC related mate choice is guided by the sense of smell in vertebrates. Parts of the heavy chains of the MHC glycoproteins are detected in various body fluids like saliva, urine and sweat. In addition, it has been suggested that MHC molecules influence microorganisms of the skin which are involved in the formation of body odours. The precise mechanisms by which those MHC molecules shape the body odor are still under discussion. However, MHC determined odors activate vomeronasal and olfactory neurons.

    In humans, MHC is called human leucocyte antigen (HLA). HLA alleles are grouped into class I (encompassing amongst others HLA-A, HLA-B and HLA-C), class II (encompassing amongst others HLA-DR, HLA-DQ and HLA-DP) and class III alleles (e.g. HSP 70, TNF α and Factor B). HLA class I molecules are expressed by almost every nucleated cell in the body. Their function lies in the presentation of proteins to T cells. HLA class II molecules are located in cells of the immune system and show fragments from phagolysosomes to T cells.

    For a long time it has not been clear whether the mechanism of MHC related mate choice is evolutionarily conserved in humans. However, in 1995 it was shown that HLA similarity affects human body odour preference. In this study, 49 women preferred the body odour of HLA dissimilar men in comparison to similar men. Preference of body odours of HLA dissimilar persons has been replicated in various studies, however another study showed no impact of HLA on body odour preferences and it has been suggested that an intermediate level of HLA dissimilarity might be optimal in terms of body odour preference.

    Most of those studies examined only a few of the HLA loci (mainly -A, -B and -DR) at comparably low resolution (e.g. HLA subgroups) and for most studies, HLA similarity was no determined for each HLA loci, but a total score was analysed (for excellent overview compare).

    Taken together, those studies suggest that HLA compatibility may influence body odour preference such that dissimilar body odours are preferred over similar ones. Oral contraception may disrupt this effect11.

    It is an interesting question, how humans are able to perceive HLA related peptides. Humans have no functional vomeronasal organ, hence perception must be established through a different pathway. In fact, receptors expressed in the olfactory epithelium may be involved in this chemosensory communication and it has been shown recently that women are able to differentiate pure HLA related peptide ligands1. However, the mechanisms are not delineated yet (compare for ongoing debate).

    In animals, immunologic compatibility is a major factor in mate choice. In humans, studies show mixed effects. A study from 1983 reports that married couples shared more HLAA and -B alleles that expected by chance. However, the mixed ethnicities in this study may have caused this effect and after control of ethnicity, no effect of HLA was observed. Other studies report – in line with the animal results – that couples share fewer alleles than expected by chance and results are influenced by cultural background. To our knowledge, only one study examined whether HLA related mate choice is behaviourally relevant in humans. The authors showed in 48 couples that partners who shared few HLA alleles were more satisfied with their sex life compared to partners who shared many HLA alleles.

    We investigated whether HLA similarity affects different aspects of partnership, such as general satisfaction, sexual satisfaction and the desire to procreate with the respective partner. Further, body odour attractiveness was examined. As it has been reported, that women prefer body odours of HLA heterozygote men before homozygote ones, we additionally tested the impact of homo- and heterozygosity.


    The current investigation revealed that immunologic compatibility matters in terms of (1) partnership satisfaction, (2) sexual satisfaction, and (3) the wish to have children. Hence, subjects were generally most satisfied with their relationship if their partner exhibited a dissimilar HLA type. This effect was only evident for HLA alleles of class I, while no effect was found for class II alleles.

    In conclusion, attraction is a miracle to most of us and only some of the many factors mediating mate choice involve odours. However, within the world of human olfaction, there seems to be no perfect mate but a perfect partner and this depends on HLA match.


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