Mouse T-cell associated serine proteinase 1 degrades collagen type IV: a structural basis for the migration of lymphocytes through vascular basement membranes.

We show that CD8+ T-lymphocyte lines perferentially attach to collagen type IV and that mouse T-cell specific serine proteinase 1 (MTSP-1) preferentially degrades native basement membrane collagen type IV. In contrast, the interstitial collagen types I, II, III, V and VI appear not to be affected. The data reveal that MTSP-1 predominantly cleaves the alpha 2(IV) chain, which is found in the native triple helical structure of type IV collagen in a ratio of alpha 1(IV): alpha 2(IV) = 2:1 into small peptides. The cleavage of the alpha 2(IV) chain within the native collagen type IV molecules most likely results not only in a destabilization of single molecules but of the entire collagenous basement membrane scaffold at the site of MTSP-1 secretion.