The nature of molecular recognition by T cells

Davis SJ, Ikemizu S, Evans EJ, Fugger L, Bakker TR, van der Merwe PA. (2003), Nat Immunol. 4, 217-24

Abstract

Considerable progress has been made in characterizing four key sets of interactions controlling antigen responsiveness in T cells, involving the following: the T cell antigen receptor, its coreceptors CD4 and CD8, the costimulatory receptors CD28 and CTLA-4, and the accessory molecule CD2. Complementary work has defined the general biophysical properties of interactions between cell surface molecules. Among the major conclusions are that these interactions are structurally heterogeneous, often reflecting clear-cut functional constraints, and that, although they all interact relatively weakly, hierarchical differences in the stabilities of the signaling complexes formed by these molecules may influence the sequence of steps leading to T cell activation. Here we review these developments and highlight the major challenges remaining as the field moves toward formulating quantitative models of T cell recognition.

Key figure: The wide variation in the 2D and 3D affinities of leukocyte cell-cell recognition molecules

(Top scale) The 3D (solution) affinities measured using SPR methods⁹ are shown on a logarithmic scale. Actual K_d values (in μM) are indicated after the name of each molecule. A typical antibody-protein antigen affinity is included for comparison. (Bottom scale) The 2D affinities for the human (h) CD2-CD58¹⁰, rat (r) CD2−rat CD48¹¹and human CD28−mouse (m) B7-1¹² interactions, measured as molecules (mols) per μm², are shown directly below the values for their respective 3D affinities. The scale is colored according to whether T cells bound strongly¹⁰ (red) or very weakly¹¹ (red/blue) via the human and rat CD2 ligands, respectively, to the model bilayer system¹⁰. The 3D affinities of coreceptors for MHC ligands are much lower than that of the rat CD2−rat CD48 interaction, suggesting that the 2D affinities of coreceptor ectodomains alone will be insufficient to sustain spontaneous recognition of their MHC ligands at the cell surface.