There is reasonable evidence that genetic pressures help to insure that offspring are different in the HLA loci from the parents. The high variability of HLA molecules enlarges the kinds of pathogens that can be recognized and eliminated by an immune response within a population.

However, a disadvantage of high HLA specificity occurs during organ transplants. The body recognizes the organ as non-self, and launches an immune response against it. Proteins from HLA genes are the cause of transplant rejections, and HLA genotypes must be partially matched to improve outcomes of organ transplants.

Finally, studies on many species show that mating preference and odor is somehow related to MHC alleles. Female mice prefer to mate with males having different MHC loci. The immune advantage of MHC diversity is apparently selected for during mating.