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Role of intercellular adhesion molecule 2(ICAM-2) in the murine immune system

University of British Columbia

Intercellular adhesion molecule-2 (ICAM-2; CD102) is one of three ligands for the p2 leukocyte integrin LFA-1 (CD11a/CD18). Although ICAM-2 expression is limited to lymphocytes, monocytes, granulocytes, and endothelium, the biological role of ICAM-2 has remained unknown. In this thesis, the murine ICAM-2 cDNA was cloned in order to assist the functional investigation. Sequence analysis of both the cDNA and the genomic clone revealed that ICAM-2 is a member of the immunoglobulin superfamily. The cDNA and antibody were used to examine the role of ICAM-2 in T cell activation and leukocyte transendothelial migration. In order to examine the role of ICAM-2 in antigen presentation to T cells, murine fibroblastic L cells expressing allogeneic class II MHC (l-Ed) were transfected with the ICAM-2 cDNA and tested for the ability to stimulate splenic T cells. The expression of ICAM-2 significantly increased the stimulation of T cells in an LFA-1-dependent manner. The increased T cell response was also observed when the class II MHC and ICAM-2 were expressed in separate cells combined together. This indicated that ICAM-2 is actually transmitting a costimulatory signal rather than merely enhancing T cell adhesion to the antigen presenting cell. T cells stimulated with ICAM-2-transfected L cells expressing the class II MHC were able to respond to an allogeneic secondary stimulation. In contrast, T cells stimulated with L cells expressing only the class II MHC were not able to respond to allogeneic stimulation in the secondary response. These results indicated that ICAM-2 may provide a necessary costimulatory signal to the T cell that is required for the aversion of an anergic state. Endothelial cells transfected with the ICAM-2 cDNA were examined for the ability to assist leukocyte migration. A system was set up in which transendothelial migration could be easily quantitated. It was found that a lymphocytic cell line and bone marrow neutrophils were able to utilize ICAM-2 for the migratory process without destroying the endothelial monolayer. These results demonstrate that ICAM-2 is able to play a role in two physiological processes that are of central importance to the normal function of the immune system.

Thesis/Dissertation

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2009-04-03

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http://hdl.handle.net/2429/6768

Medical Genetics

University of British Columbia

UBCV

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