The interaction between integrin lymphocyte function-associated antigen-1 (LFA-1) and its ligand intercellular adhesion molecule-1 (ICAM-1) is critical in immunological and inflammatory reactions but, like other adhesive interactions, is of low affinity. Here, multiple rational design methods were used to engineer ICAM-1 mutants with enhanced affinity for LFA-1. Five amino acid substitutions 1)...

Over 20% of cancer patients will suffer metastatic spread to the brain, and prognosis remains poor. Communication between tumour cells and host tissue is essential during metastasis, yet little is known of the processes underlying such interactions in the brain.Here we test the hypothesis that cross-talk between tumour cells and host brain cells, through tumour cell leukocyte function associate...

LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) are members of the beta2 integrins involved in leukocyte function during immune and inflammatory responses. We aimed to determine a minimized beta2 subunit that forms functional LFA-1 and Mac-1. Using a series of truncated beta2 variants, we showed that the subregion Q23-D300 of the beta2 subunit is sufficient to combine with the alphaL and alphaM subun...

Macrophages activated and primed in vivo, although not resident or responsive macrophages, express the lymphocyte function associated (LFA)-1 antigen. By contrast, the biochemically related Mac1 antigen is expressed on all populations of macrophages. In the present paper, we studied regulation of the LFA-1 antigen in vitro. LFA-1 could be induced in vitro n thioglycollate (TG)-elicited but not ...

We show that the LFA-1 molecule on T cells does not play a role in the stimulation of T cell hybridomas by certain targets, namely antigen presented by L cell derivatives or polyvalent anti-receptor antibody. These results suggest that LFA-1 may act by binding to ligands that are not present on all cells. We hope this result will help us and others to establish the true role of LFA-1 in T cell ...

Four children with an immunodeficiency involving the absence of leukocyte membrane glycoproteins reacting with anti-LFA-1 and OKM-1 monoclonal antibodies were unable to mediate adherence-dependent leukocyte functions. Even with normal Fc receptor function, their PMN-ADCC and MC-NKC were markedly deficient. Single cell analysis demonstrated deficient antibody-mediated PMN-target cell adherence. ...

Antigen-presenting cells (APCs) activate T cells by forming a specialized contact site called the immunological synapse (IS). The T cell receptor (TCR) and its downstream signaling molecules cluster in the center of the IS, surrounded by a ring of integrin molecules such as LFA-1, which lower the threshold for T cell priming by both tightly adhering to ligands on the surface of the APC and by a...

The interaction of lymphocyte function-associated antigen-1 (LFA-1) with its ligands mediates multiple cell adhesion processes of capital importance during immune responses. We have obtained three anti-ICAM-3 mAbs which recognize two different epitopes (A and B) on the intercellular adhesion molecule-3 (ICAM-3) as demonstrated by sequential immunoprecipitation and cross-competitive mAb-binding ...

Large granular lymphocytes, mediators of NK activity, bind to other cells using both the LFA (lymphocyte function-associated)-1-ICAM and the CD2-LFA-3 adhesion pathways. Here we have studied the motility and ultrastructure of large granule lymphocyte (LGL) on lipid bilayers containing purified LFA-1, ICAM-1, and the transmembrane and glycophosphatidylinositol isoforms of LFA-3. LGLs moved at 8 ...

Lymphocyte function-associated antigen 3 (LFA-3)' is a widely distributed cell surface glycoprotein that is a ligand for the T lymphocyte CD2 glycoprotein (1-4). This receptor-ligand pair is used in many intercellular adhesion interactions, including binding ofcytolytic Tlymphocytes to target cells (3) and thymocytes to thymic epithelial cells (4). Both CD2 and one form ofLFA-3 have membrane-sp...