Evolutionary simulations of Z -linked suppression gene drives

Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on using Z -linked gene drives to control species with ZW sex determination, which include Lepidopteran pests, parasitic trematodes, and cane toads. These proposals include Z -linked ‘ W -shredders’, which would suppress populations by cleaving the W chromosome and causing females to produce only sons, as well as Z -linked female-sterilizing gene drives. Here, I use eco-evolutionary simulations to evaluate the potential of some proposed Z -linked gene drives, and to produce recommendations regarding their design and use. The simulations show that W -shredders are likely to be highly effective at eradicating populations provided that resistance to W -shredding cannot evolve. However, W -shredder alleles can invade populations from very low frequencies, making it difficult to eliminate specific populations while leaving nearby populations untouched; this issue may restrict their possible uses.

Identification, immunomodulatory activity, and immunogenicity of the major helper T-cell epitope on the K blood group antigen

The K blood group remains an important target in hemolytic disease of the newborn (HDN), with no immune prophylaxis available. The aim was to characterize the Th response to K as a key step in designing specific immunotherapy and understanding the immunogenicity of the Ag. PBMCs from K-negative women who had anti-K Abs after incompatible pregnancy, and PBMCs from unimmunized controls, were screened for proliferative responses to peptide panels spanning the K or k single amino acid polymorphism. A dominant K peptide with the polymorphism at the C terminus elicited proliferation in 90% of alloimmunized women, and it was confirmed that responding cells expressed helper CD3+CD4+ and “memory” CD45RO+ phenotypes, and were MHC class II restricted. A relatively high prevalence of background peptide responses independent of alloimmunization may contribute to K immunogenicity. First, cross-reactive environmental Ag(s) pre-prime Kell-reactive Th cells, and, second, the K substitution disrupts an N-glycosylation motif, allowing the exposed amino acid chain to stimulate a Th repertoire that is unconstrained by self-tolerance in K-negative individuals. The dominant K peptide was effective in inducing linked suppression in HLA-transgenic mice and can now be taken forward for immunotherapy to prevent HDN because of anti-K responses.