A Review of Suggested Mechanisms of MHC Odor Signaling

Simple Summary Immune genes of the vertebrate MHC vary among individuals. Each individual collection is optimally diverse to provide resistance against some infectious diseases but not too diverse to cause autoimmune diseases. MHC-dependent mate choice aims for optimally complementary MHC alleles. Each potential partner signals through body odor his/her MHC alleles. Identifying the signal molecules was a long-lasting puzzle solved only recently after many deviations as described. Commensal microbiota which are controlled by the individual MHC genes differ among individuals. They were suspected repeatedly to provide the signal, though mice raised germ-free could still smell MHC genes. Carrier hypotheses came in various versions, centered around the specificity of each MHC molecule for binding peptides from diseases, shown to T lymphocytes to induce the immune response. Volatiles of various origins were suggested to fill the place of the peptide and thus reflect the identity of the MHC molecule. Finally, the bound peptides themselves were identified as the sought info-chemicals. Synthesized peptides affect mate choice as predicted. Specific olfactory neurons were shown to react to these peptides but only to the anchors that define the binding specificity. Even eggs choose sperm to produce offspring with optimal MHC, though the signaling pathway needs further research. Although an individual's mix of MHC immune genes determines its resistance, finding MHC-dependent mate choice occurred by accident in inbred mice. Inbred mice prefer MHC dissimilar mates, even when the choice was restricted to urine. It took decades to find the info-chemicals, which have to be as polymorphic as the MHC. Microbiota were suggested repeatedly as the origin of the odor signal though germ-free mice maintained normal preference. Different versions of the 'carrier hypothesis' suggested MHC molecules carry volatiles after the bound peptide is released. Theory predicted an optimal individual MHC diversity to maximize resistance. The optimally complementary mate should be and is preferred as several studies show. Thus, the odor signal needs to transmit the exact information of the sender's MHC alleles, as do MHC ligand peptides but not microbiota. The 'MHC peptide hypothesis' assumes that olfactory perception of the peptide ligand provides information about the MHC protein in a key-lock fashion. Olfactory neurons react only to the anchors of synthesized MHC peptides, which reflect the binding MHC molecule's identity. Synthesized peptides supplemented to a male's signal affect choice in the predicted way, however, not when anchors are mutated. Also, the human brain detects smelled synthesized self-peptides as such. After mate choice, the lottery of meiosis of randomly paired oocyte and sperm haplotypes would often produce MHC non-optimal offspring. In sticklebacks, eggs select MHC-compatible sperm, thus prefer the best combination close to the population optimum.