Characterization of urinary peptides: In search of MHC-dependent olfactory cues
Mating experiments with inbred and congenic lines performed in the late seventies suggested that individual recognition in mice is influenced by Major Histocompatibility Complex (MHC)-dependent olfactory cues. Extensive training experiments indicated that the relevant components are volatiles present in urine but in spite of considerable efforts in several laboratories no consensus view as to their identity has emerged. On the other hand, recent work suggests that typical MHC-binding peptides are recognized with high affinity by sensory neurons in the vomeronasal as well as the main olfactory organ and are able to elicit the pregnancy block in female mice (Bruce effect). However, it remains unknown whether such peptides in fact occur in mouse urine. The current knowledge on the composition of the cellular peptidome indicates its MHC dependency, suggesting that also peptide populations in the extracellular space, including body fluids, should be MHC dependent. If this hypothesis turns out to be correct, the consequences would touch not only the olfaction field but the entire field of peptide biomarker analysis. Therefore, we propose in this application to search for MHC-dependent urinary peptides in mice, first by looking for specific peptides, and second via the characterization of the entire urinary peptidome. Candidate peptides can subsequently be tested for their interaction with neurons in olfactory epithelia as well as in behavioural experiments. In parallel, we will start inital experiments to explore the hypothesis on MHC dependency of the urinary peptidome also in humans.