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Lymphocyte function associated antigen 1 (LFA-1) is a heterodimer, composed of an α L-chain and a β 2-chain. The I-domain is inserted in the ctL-chain and contains a binding site for ICAM-1. To study the adhesive interaction between the I-domain and ICAM-I, we constructed a GPIanchored form of the I-domain and expressed it stabily in BHK-cells. In contrast to the whole LFA-1 molecule (Kd=8nM), no interaction between soluble ICAM-1 dimers and I-domain expressing cells could be detected, suggesting that the ICAM-1/I-domain interaction is of low affinity (Kd>33|<M). In flow cell experiments the I-domain expressing cells rolled on glass supported planar bilayers containing ICAM-1. Rolling was not caused by an uprooting of the GPI-linked protein, since BHK-cells expressing GPI-anchored ICAM-1 attached stabily to bilayers containing purified LFA-1. The interaction between ICAM-1 and the I-domain is dependent on divalent cations and is blocked by the LFA-1 function blocking monoclonal antibody TS1/22. Binding of the activating antibody MEM-83 to the I-domain resulted in a decreased rolling velocity on ICAM-1 containing bilayers. These experiments suggest that the I-domain interaction with ICAM-1 can be modulated by conformational changes in the I-domain. In all cases, the 1-domain bound to ICAM-1 with low affinity, fast off-rate and resistance to dissociation by bond strain. Therefore it is most likely, that the I-domain cooperates with other ICAM-1 binding site(s) in LFA-1 to allow high affinity binding of ICAM-1.


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