Frank Eggert

Olfactory cues associated with the major histocompatibility complex

Besides its immunological function of self/non‐self discrimination the major histocompatibility complex (MHC) has been recognized as a possible source of individual specific body odors. Dating back to speculations on the role of the extraordinary polymorphism of the MHC as background of an individual chemosensory identity and to early observations of MHC‐dependent mate choice in inbred strains of mice, systematic experimental studies revealed a first evidence for H‐2 related body odors in this species. Meanwhile a large number of animal studies with rodents and a series of field studies and experiments with humans have extended our knowledge of MHC‐related odor signals and substantiated the hypothesis of immunogenetic associated odortypes. These results suggest that the most prominent feature of the MHC, its extraordinary genetic diversity, seems in part to be selectively maintained by behavioral mechanisms which operate in contemporary natural populations. The high degree of heterozygosity found in natural populations of most species seems to be promoted by non‐disease‐based selection such as mating preferences and selective block of pregnancy.

MHC-Related Odors in Humans

Up to now, MHC-related odors have been only described for rodents Yamazaki et al., 1991; Roser et al., 1991). Nevertheless, it has been speculated that a similar phenomenon may also occur in humans (Beauchamp et al., 1985; Boyse et al., 1987). Individual specific body odors do indeed play a role in human self-perception (Porter and Moore, 1981; Lord and Kasprzak, 1989) and recognition of offspring (Porter et al., 1983; Kaitz et al., 1987), but there is no information available on the biological basis of these odors.

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

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.

Fractionation and bioassay of human odor types

Human urine samples were fractionated to examine the contribution of volatiles to the individual body odor. The samples were obtained from 4 male donors and fractionated using a vacuum technique. The volatiles from the chemical fractions were analyzed using the CLSA technique and gas chromatography. Thereafter, these fractions were tested in a computer-controlled olfactometer by trained rats. Although the rats were able to discriminate the distillation residue, they could not recognize the urine odor in the distilled fraction. The results of gas chromatography indicate a continuous release of volatile constituents in the distillation residue.

MHC and Olfactory Communication in Humans

Descriptive results from three field studies concerned with a possible association between genetical similarity with regard to the MHC and the hedonics of body odors as well as the degree of acquaintance yielded a similar pattern of results: The similarity in class I HLA-A and HLA-B alleles appears to be associated with the hedonics of another person’s body odor and with the degree of acquaintance or familiarity between persons. The direction of these associations appear to depend on whether the persons are of the same sex or of opposite sexes. Repeated measurements of the degree of acquaintance point to the conclusion that formation of groups and social choice between people may be influenced by their HLA-similarity.

Perception of HLA-Related Body Odors During the Course of the Menstrual Cycle

In the present study chemosensory event-related potentials (CSERP) were used to find objective evidence that body odor and the perception of body odor by females is related to the similarity of the Major Histocompatibility Complex (HLA in humans) of the subject and donor. Ten female subjects were examined three times during the course of their menstrual cycle (follicular, ovulatory and luteal phase). During a test session the responses of subjects to the odors of either three male or three female donors was measured. The HLA types of two donors were similar to each other but different to the HLA type of the test subject and the third donor, who shared a similar HLA type. Chemosensory event-related potentials were recorded from 7 electrode sites on the skull (Fz, Cz, Pz, F3, F4, P3, P4), referred to linked mastoids. Preliminary results show that during the ovulatory cycle phase, subjects responded with larger amplitudes to body odors of male donors with a similar HLA-type than to odors of male donors with a dissimilar HLA-type. When female odors were presented the speed of the neural response changed with the HLA-type of the odor donor during the luteal phase only.

GC Profiles of Volatile Constituents from Human Urine Obtained by Closed Loop Stripping, Purge and Trap Technique and Simultaneous Steam Distillation-Extraction

Abstract Different techniques like “closed loop stripping” [CLSA], “purge and trap” [PTI], and continous steam distillation extraction [SDE] were used to establish GC profiles of major histocompatibility complex-associated volatile constituents of human urine and statistically evaluated for reliability. Of the three methods investigated, PTI appeared to be superior for the detection of very volatile substances, whereas SDE was the most efficient one with respect to yield. A number of short to medium-chain ketones, 4-hydroxy-3-methoxy-styrene, menthol and nicotine were identified in preliminary analyses.

MHC-Associated and MHC-lndependent Urinary Chemosignals in Mice Are Expressed via the Hematopoietic System

The change in genetically determined urine odors which appears after experimental bone marrow transplantations in mice was examined in order to test whether the HMC is the only group of genes that influences the chemosensory identity via the hematopoietic system. 5 female rats were trained in a computer-controlled olfactometer to discriminate urine odors of two MHC congenic or background congenic inbred strains of mice. Transfer-of-training tests with urine samples of irradiated mice which were restored with bone marrow either from an MHC congenic or a background congenic inbred strain reveal a change of urinary chemosignals after both types of experimental bone marrow transplantation. Thus, both MHC-associated as well as MHC-independent urinary chemosignals are expressed via the hematopoietic system.

Functional Relationship between the Olfactory and Immune Systems

The development of psychoneuroimmunology has changed our view of the immune system, which has been thought of as an autonomous system within the organism. Results from psychoneuroimmunology have brought us to the conclusion that the immune system interacts with the neural as well as the endocrine system. Therefore, the immune system is now understood as being an integrative part of the organism acting on other systems and being influenced by them.

Pathophysiologically correlated deficits of information processing in obstructive sleep apnea patients

In obstructive sleep apnea patients, who intermittently stop breathing at night for some seconds, functions of vigilance and attention seem to be impaired. The aim of our study was to investigate if nocturnal hypoxia as one possible detrimental factor is associated with the degree of modality shift effect expressing attention function at a very basic level of information processing. For the first time an experimental approach was applied to examine attention deficits in sleep apnea patients. Correlation analyses between pathophysiological parameters and attention function revealed a stronger association for the modality shift effect than for simple reaction times.