Fig. 5.

Rapidly-evolving positions in CD1a are sufficient to modulate predicted affinity for lipid antigens. (A) Mutation of site 98 to tryptophan in human CD1a (olive baboon and crab-eating macaque share this amino acid at this position) results in increased predicted binding affinity to DDM, with overall fold increase between endogenous ligand and DDM. Mutation of tryptophan at site 98 in crab-eating macaque to ancestral glycine results in higher binding affinity for all endogenous ligands tested, and loss of feasible lipid-swapping and DDM presentation. (B) Mutation of site 98 to tryptophan in snub-nosed monkey CD1a results in increased predicted binding affinity to DDM. Colobus, which is not predicted to swap endogenous ligand for DDM, also increases spread between binding affinities. In colobus, however, it is a decrease in affinity for endogenous lipid rather than increase in DDM affinity that is responsible for the fold change.