Regulated cell adhesion is critical for most immune functions. Integrins are one of the more important families of adhesion molecules, and Lymphocyte Function-Associated Antigen-1 (LFA-1) is the most abundant beta2 integrin. The purpose of this proposal is to examine the regulatory mechanisms of LFA-1 adhesiveness for intercellular Adhesion Molecule 1 (ICAM-1). Cells expressing constitutively active or non- active LFA-1 will be prepared by retroviral mutagenesis and selected for the desired phenotype. This type of mutagenesis links a phenotype (active or non-active LFA-1) to the genotype. Thus, a gene that has been disrupted by a retrovirus and causes a particular phenotype can be identified. Understanding how lymphocytes regulate adhesion will lead to new therapeutic strategies for controlling inflammation and possibly autoimmune diseases and the rejection of organ transplants.
| Cherry, Lisa K; Li, Xiaoyu; Schwab, Pascale et al. (2004) RhoH is required to maintain the integrin LFA-1 in a nonadhesive state on lymphocytes. Nat Immunol 5:961-7 |
