Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.
ISOLATION AND CHARACTERIZATION OF THE GENE ENCODING T4 (CD4): A RECEPTOR MEDIATING CELL-CELL AND CELL-HIV INTERACTIONS (IMMUNODEFICIENCY)
Diss Abstr Int [B]; 50(1):163 1989. Unique Identifier : AIDSLINE ICDB/90658139 Maddon PJ; Columbia Univ.
Abstract:
The surface glycoproteins T4 (CD4) and T8 (CD8) define different functional subsets of T lymphocytes and may act as recognition molecules mediating appropriate interactions between the T cell and its target. T4 may also serve as a receptor for HIV. The elucidation of the structure of the T4 glycoprotein and its role in both T-cell-target cell interactions and HIV infection is likely to be facilitated by the isolation of the gene encoding T4, the determination of its sequence, structure, and expression patterns, and the introduction of the T4 gene into different cellular environments. We have therefore isolated cDNA and genomic clones encoding T4 and the murine homolog, L3T4. The protein sequence and predicted molecular structure reveal that T4 is a member of the immunoglobulin gene family and exhibits a polyimmunoglobulin-like structure on the cell surface. The T4 gene consists of a collection of exons conserved in several members of the immunoglobulin gene family, suggesting that T4 is a primitive immunoglobulin gene. In addition, the T4 gene is expressed in a broad range of cell types, implying that T4 plays a more general role in mediating cell recognition events that are not restricted to the cellular immune response. We have developed a model system to examine the role of T4 in T cell function. These studies indicate that the interaction of T4 with class II MHC proteins is essential for efficient T cell function. We have also performed experiments which demonstrate that T4 is the receptor for HIV and that the mere presence of T4 on the cell surface is sufficient to render both human lymphoid and nonlymphoid cells susceptible to HIV infection. In addition, we have demonstrated that HIV infection does not require T4 endocytosis. Finally, we have produced a soluble form of T4 (sT4) which inhibits the binding of HIV to T4+ cells, resulting in a striking inhibition of infectivity. The ability of sT4 to inhibit HIV infection in vitro suggests the potential use of sT4 as an antiviral agent in AIDS patients. The generation of sT4 mutants has permitted us to delineate the precise location of the HIV binding site. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD89-06048)
Keywords: Acquired Immunodeficiency Syndrome/*GENETICS Antigens, CD4/*GENETICS/ISOLATION & PURIF *Gene Expression Regulation, Viral Human HIV/*GENETICS Receptors, HIV/*GENETICS/ISOLATION & PURIF T-Lymphocytes THESIS 900228
M9020579
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Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.
