A population-genetic model in which infectious diseases impose independent density-dependent regulation on whole HLA haplotypes rather than single alleles. A guild of specialised haplotypes with incomplete peptide recognition, separated by limiting similarity, reaches a stable range of steady-state densities where effective fitnesses vanish, so haplotype frequencies themselves rank fitness and the resulting interrelated haplotype network becomes the origin of balancing selection maintaining MHC/HLA polymorphism.
The human MHC/HLA transplantation loci are the most polymorphic in the genome, and existing explanations (heterozygote advantage, negative frequency-dependent selection) act on individual alleles. Th…