Discrimination of MHC-derived odors by untrained mice is consistent with divergence in peptide-binding region residues

Abstract

Genes of the major histocompatibility complex (MHC) play a central role in immune recognition, yet they also influence the odor of individuals. Mice can be trained to distinguish odors mediated by classical MHC loci; however, training can introduce confounding behavioral artifacts. This study demonstrates that mice can distinguish some, but not all, naturally occurring allelic variants at classical MHC loci without prior training. This result suggests that MHC-disassortative mating preferences might operate by means of small MHC-based odor differences, and could therefore contribute to diversifying selection acting on MHC loci. Here we show that odors of two MHC mutant mouse strains (bm1 and bm3) can be distinguished, even after genetic background is controlled by intercrossing strains. These two strains differ by five amino acids, three of which are predicted to chemically contact peptides bound to the peptide-binding region (PBR), the site of antigen presentation for T cell recognition. However, the odors of neither bm1 nor bm3 were distinguished from their parental B6 haplotype after randomizing genomic background, despite discrimination of purebred B6 and bm1 strain odors. These combined results suggest that (i) there may be an MHC odor discrimination threshold based on divergence in PBR residues, providing a more logical pattern of MHC-based odor discrimination than found in previous training studies, where discrimination ability was not correlated with PBR divergence; and (ii) additional (non-MHC) mutations that influence odor have accumulated in these strains during the 100 generations of divergence between pure B6 and bm1 strains.

Olfactory Fingerprints for Major Histocompatibility Complex-Determined Body Odors II: Relationship among Odor Maps, Genetics, Odor Composition, and Behavior

“…In contrast with Yamazaki et al (1983), Carroll et al (2002 failed to find a discrimination between urines from F 2 C57BL/6-H-2 b (b) versus C57BL/6-H-2 bm1 (bm1) animals. In the Yamazaki et al (1983) study, all F 2 data were obtained from mice whose only training was on b versus bm1-inbred urines.…”

“…6, Table 1) (Yamazaki et al, 1990). The behavioral discrimination data were obtained using y-maze experiments (see also Carroll et al, 2002). It is assumed that the more difficult it is to discriminate two odorants, the more training trials are required to reach the performance criterion (80% correct responding).…”

Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons

“…In the first one, the MHC has been considered to influence the volatile composition of urine, as demonstrated by habituation, training and other tests with MHC congenic or mutant inbred strains [9][10][11][12][13][14][15] . Analysis of urinary volatiles of single inbred mice showed considerable variation in the abundance of certain volatiles.…”

Detective mice assess relatedness in baboons using olfactory cues

“…Previous studies, essentially in rodents, indicate that the scents associated with the MHC can be used to recognise kin (Yamazaki et al, 1983;Roser and Singh, 1991;Potts et al, 1991;Manning et al, 1992;Brennan and Peele, 2003), although similar effects are not documented in baboons. The MHC is a highly polymorphic gene complex that has been shown to influence the volatile scent profiles of mice (Yamazaki et al, 1979;Carroll et al, 2002), rats (Singh et al, 1987) and humans (Wedekind and Furi, 1997;Jacob et al, 2002). It is thus possible that individual odour differences perceived by mice result from MHC variation among individuals.…”