A Molecular Model of CD86 and Analysis of Mutations which Disrupt Receptor Binding

CD86 and its homologue CD80 are type I transmembrane proteins expressed on antigen presenting cells. CD80 and CD86 specifically interact with CD28 and CD152 on T cells. This interaction results in T cell costimulation and complements T cell receptor signaling. The extracellular regions of CD80 and CD86 contain two immunoglobulin-like domains. In the presence of low sequence similarity to proteins with known three-dimensional structure, a molecular model of the N-terminal receptor-binding domain of human CD86 was built based on consensus residue analysis and structure-oriented sequence comparison. The model was assessed by energy profile analysis and regions of high, medium, and low prediction confidence were identified. Several CD86 point mutations which abolish receptor binding map to high confidence regions of the model. This has made it possible to rationalize their effects on binding or structure.