tested the hypothesis of a conserved activation mode of monocytic THP-1 cells by proteins I/II expressed by several species of oral streptococci through the specific role of the extended V-region. We studied the binding and modulating activities of six proteins I/II purified from strains representing four different species of oral streptococci, and of expression products of polymerase chain reaction-amplified sequences encoding corresponding extended V-regions, We found that the different proteins I/II bound to THP-1 cells in a sugar-dependent mode involving the extended V-region. Furthermore, all the proteins I/II stimulated THP-1 cells to produce tumor necrosis factor a, indicating that these properties are not strain- or species-specific. Despite the weak: stimulation of THP-1 cells by the extended V-region alone, we obtained evidence that cross-linking of this region can be one of the mechanisms involved in monocytic cell activation by proteins I/II.