Collagens serve as an extracellular store of bioactive interleukin 2

The binding of certain growth factors and cytokines to components of the ex tracellular matrix can regulate their local availability and modulate their biological activities. We show that interleukin 2 (IL-2), an important sti mulator of T cell growth, preferentially binds to collagen types I, III, an d VI and to a lesser degree to collagen types II, IV, and V, immobilized on polystyrene or nitrocellulose. These interactions are inhibited by denatur ed, single collagen chains or a subset of their cyanogen bromide peptides i n a dose-dependent manner. Cross-inhibition experiments and ligand blotting of collagen-derived peptides point to a limited set of collagenous consens us sequences mediating the binding of IL-2. This interaction is saturable, with dissociation constants of similar to 10(-8) M, and estimated molar rat ios of 4-6 molecules of IL-2 bound to one molecule of triple helical collag en. Furthermore, collagen-bound IL-2 stimulates proliferation of mouse lymp hocytes. We conclude that its specific binding to the abundant interstitial collagens leads to a spatial pattern of bioavailable IL-2 which is dictate d by the local organization of the collagenous extracellular matrix. This i nteraction may contribute to the particular phenotype of stromal lymphocyte s and could be exploited for devising collagenous peptide analogues that mo dulate IL-2 bioactivity.