Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (Ph. D.)--University of Virginia, 2006. / Includes bibliographical references (leaves 109-130). Also available online through Digital Dissertations.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (M.S.)--University of Delaware, 2006. / Principal faculty advisor: Carlton R. Cooper, Dept. of Biological Sciences. Includes bibliographical references.

CD44 is a transmembrane glycoprotein found on a variety of cells including those of myeloid and lymphoid origin. CD44 is highly conserved among various species and is involved in the homing of lymphocytes and monocytes to lymph nodes, Peyer's patches, and sites of inflammation. In the present study, we demonstrate that monoclonal antibody (mAb) 9F3, directed against murine CD44 expressed on cytotoxic T lymphocytes (CTls), can trigger the lytic activity of CTls and redirect CTl-mediated lysis to antigen-negative Fc receptor-positive target cells. Similar redirected lysis was also inducible using mAb MEL - 14, directed against the lymphocyte homing receptor for endothelium (gp - 90MEL-14). The redirected lysis induced by mAbs 9F3 and MEl-14 in the CTL was similar to that induced by mAbs against the aβ T-cell receptor or CD3. In contrast, mAbs directed against CDS, CD45R, and CD11a (LFA-1, lymphocyte function-associated antigen 1) failed to evoke lytic activity. Furthermore, CD44 and MEl-14 mAbs were able to mediate NK cell lysis of the NK-resistant tumor PS15. The current study demonstrates that CD44 and gp_90MEL-14 molecules, in addition to participating in T-cell homing and adhesion, may play a major role in delivering the transmembrane signal to the CTl that triggers the lytic activity, even when the T cell receptor is not occupied. The alternate pathway of CTL activation characterized in this study may exhibit both beneficial and deleterious effects on the host. On one hand, this property may enable CTL to kill cancer cells or virally-infected cells which may fail to express major histocompatibility complex (MHC)-encoded antigens. On the other hand, this alternate pathway may contribute to nonspecific tissue damage seen at sites of inflammation. / Master of Science

During hemostatic and inflammatory responses, cell adhesion molecules play a major role in regulating the leukocytes and platelets adhesion to vascular surfaces under the hydrodynamic environment of the circulation. Selectin-ligand interactions (bonds) mediate leukocyte rolling on vascular surfaces. The molecular basis for differential ligand recognition by selectins is poorly understood. Using atomic force microscopy (AFM), the kinetics of three mutants L-selectin interacting with surrogates of PSGL-1 and PNAd, is compared with those of wild-type L-selectin. The interaction between glycoprotein Ib (GPIb) and von Willebrand Factor (VWF) mediates platelet translocation at the vascular vessel damage sites, which plays a critical role in initiating the platelets adhesion and thrombus formation. Translocation of platelets on VWF requires a shear threshold, suggesting a possible catch bond at work there. We characterized the kinetics of GPIbα interacting with VWF A1 domain, confirming the catch bond existed. Two type 2B VWD A1 mutants eliminated the catch bond and gave longer low force lifetimes. The prolonged lifetimes at low force resulted in more agglutination of platelets with A1 coated microspheres in flow. During the process of hemostasis, the size of prothrombotic ULVWF affects the affinity of VWF to platelets bearing GPIbα on the membrane. ADAMTS13 has been identified and characterized as a multi-domain metalloprotease that regulate the size of ULVWF. We studied how force regulated the binding and cleavage of ADAMTS13 on VWF. We found the cleavage effects could only be observed after the catastrophic structural change of A1A2A3. The unfolding exposed the ADAMTS13 cleavage site and favored the cleavage. Two protocols using different stretching molecules (GPIbα and CR1) and A1A2A3 immobilization methods revealed the cleavage effects diminished with increasing stretching force. This study elucidated mechanisms of the binding kinetics of L-selectin with different structure components from PSGL-1 and PNAd by structural variants. It also provided new insights into our current knowledge of the dynamic adhesion and regulation of GPIbα-VWF interaction in vivo. Using single molecule method, the chemical catalytic reaction between enzyme and substrate has been targeted. These results help us understand this important enzyme-substrate interaction involved in the hemostasis.

Thesis (Ph.D.). / Written for the Dept. of Biology. Title from title page of PDF (viewed 2008/02/12). Includes bibliographical references.

Thesis (Ph. D.)--School of Pharmacy and School of Dentistry. University of Missouri--Kansas City, 1998. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [106]-127).