Molecular cloning and characterization of CD4 in an aquatic mammal, the white whale Delphinapterus leucas

Given the importance of the cell surface recognition protein, CD4, in immun e function, the cloning and characterization of CD4 at the molecular level from an odontocete cetacean, the white whale (Delphinapterus leucas), was c arried out. Whale CD4 cDNA contains 2662 base pairs and translates into a p rotein containing 455 amino acids. Whale CD4 shares 64% and 51% identity wi th the human and mouse CD4 protein, respectively, and is organized in a sim ilar manner. Unlike human and mouse, however, the cytoplasmic domain, which is highly conserved, contains amino acid substitutions unique to whale. Mo reover, only one of the seven potential N-linked glycosylation sites presen t in whale is shared with human and mouse. Evolutionarily, the whale CD4 se quence is most similar to pig and structurally similar to dog and cat, in t hat all lack the cysteine pair in the V2 domain. These differences suggest that CD4 may have a different secondary structure in these species, which m ay affect binding of class II and subsequent T-cell activation, as well as binding of viral pathogens. Interestingly, as a group, species with these C D4 characteristics all have high constituitive expression of class II molec ules on T lymphocytes, suggesting potential uniqueness in the interaction o f CD4, class II molecules, and the immune response, Molecular characterizat ion of CD4 in an aquatic mammal provides information on the CD4 molecule it self and may provide insight into adaptive evolutionary changes of the immu ne system.