Evidence of continuous evolutionary change in structures mediating adherence of lymphocytes to specialised venules

Abstract

MANY cell–cell interactions are similar in a wide variety of species; for instance, penetration of ova by spermatozoa, morphogenetic cell movements during embryogenesis, and specific cellular cooperation during the immune response in vertebrates. The operation of apparently identical functional interactions in diverse species, however, does not exclude the possibility that the cell surface receptors and ligands involved may have changed considerably during evolution. In fact, studies of the molecular evolution of certain enzymes and proteins present in numerous species have demonstrated that structural evolutionary change (that is, amino acid substitutions) may proceed even in the absence of observed functional modification¹. For this reason, we suggest that the investigation of the degree of evolutionary change in structures mediating conserved cell–cell interactions requires determination of the degree to which the interaction is possible between cells from different species. The present study was designed to examine quantitatively the effect of progressive evolutionary divergence on interspecies cellular cooperation in a simple, highly conserved cell–cell interaction: the specific adherence of lymphocytes to specialised lymphocyte-binding high endothelial venules (HEV) in lymph nodes. Based on results of quantitative in vivo and in vitro assays, we report that the ability of lymphocytes from different vertebrate species to recognise specifically and bind to HEV in the mouse declines exponentially with increasing evolutionary separation of the lymphocyte donor from the mouse host. This suggests that, in spite of conservation of the functional interaction in all mammalian species examined², the cell-surface structures mediating lymphocyte adherence to HEV have been continuously and randomly altered during evolution.