Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors

Interaction between CD2 and its counterreceptor, CD58 (LFA-3), on opposing cells optimizes immune recognition, facilitating contacts between helper T lymphocytes and antigen-presenting cells as well as between cytolytic effec ters and target cells. Here, we report the crystal structure of the heterop hilic adhesion complex between the amino-terminal domains of human CD2 and CD58. A strikingly asymmetric, orthogonal, face-to-face interaction involvi ng the major beta sheets of the respective immunoglobulin-like domains with poor shape complementarity is revealed. In the virtual absence of hydropho bic forces, interdigitating charged amino acid side chains form hydrogen bo nds and salt links at the interface (similar to 1200 Angstrom(2)), impartin g a high degree of specificity albeit with low affinity (K-D of similar to mu M). These features explain CD2-CD58 dynamic binding, offering insights i nto interactions of related immunoglobulin superfamily receptors.