ACTIVATED CONFORMATIONS OF VERY LATE ACTIVATION INTEGRINS DETECTED BYA GROUP OF ANTIBODIES (HUTS) SPECIFIC FOR A NOVEL REGULATORY REGION (355-425) OF THE COMMON BETA-1-CHAIN

The very late activation antigens (VLA) or beta 1 integrins mediate ce ll attachment to different extracellular matrix proteins and intercell ular adhesions. The ligand binding activity of these adhesion receptor s is not constitutive and can be regulated by temperature, presence of extracellular divalent cations, stimulatory monoclonal antibodies (mA bs), and cellular activation. We have generated three novel mAbs, HUTS -4, HUTS-7, and HUTS-21, recognizing specific epitopes on the common b eta 1 subunit (CD29) of VLA integrins whose expression correlates with the ligand binding activity of these heterodimeric glycoproteins. Thi s correlation has been demonstrated for several integrin heterodimers in different cell systems using a variety of extracellular and intrace llular stimuli for integrin activation. Thus, the presence of micromol ar concentrations of extracellular Mn2+, preincubation with the activa ting anti-beta 1 mAb TS2/16, and cell treatment with phorbol esters or calcium ionophores, induced the expression of the HUTS beta 1 epitope s on T lymphoblasts. Using a panel of human-mouse beta 1 chimeric mole cules, we have mapped these epitopes to the 355-425 sequence of the be ta 1 polypeptide. This segment represents therefore a novel regulatory region of beta 1 that is exposed upon integrin activation. Interestin gly, binding of HUTS mAbs to partially activated VLA integrins results in maximal activation of these adhesion receptors and enhancement of cell adhesion to beta 1 integrin ligands collagen, laminin, and fibron ectin.