CD4 dimerization and oligomerization: implications for T-cell function and structure-based drug design.

S Li; T Satoh; R Korngold; Z Huang

doi:10.1016/s0167-5699(98)01325-5

Home/Archive/PubMed

PubMed · 9785669

CD4 dimerization and oligomerization: implications for T-cell function and structure-based drug design.

S Li·T Satoh·R Korngold·Z Huang

View original source ↗Export metadata ↓

Abstract

Recent studies of CD4 structure and function have revealed possible mechanisms for CD4 self-association, with implications for its role in T-cell activation. Here, the authors discuss the formulation of a hypothetical three-dimensional model of CD4 oligomerization and how it impacts on the understanding of T-cell function and rational drug design targeting specific CD4 surface functional sites.

Explore related subjects

CD4 Antigens Dimerization Drug Design Humans Lymphocyte Activation Major Histocompatibility Complex Models, Chemical Models, Immunological Receptors, Antigen, T-Cell Structure-Activity Relationship T-Lymphocytes Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

S Li, T Satoh, R Korngold, Z Huang. 1998. CD4 dimerization and oligomerization: implications for T-cell function and structure-based drug design.. https://doi.org/10.1016/s0167-5699(98)01325-5

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2000

HIV-1 membrane fusion: targets of opportunity.

Explore the source record for details and available documents.

CD4 Antigens↗

PubMed2000

Exploitation of cellular signaling by HIV-1: unwelcome guests with master keys that signal their entry.

Explore the source record for details and available documents.

CD4 Antigens↗

PubMed2000

Lactoferrin upregulates the expression of CD4 antigen through the stimulation of the mitogen-activated protein kinase in the human lymphoblastic T Jurkat cell line.

The main biological properties of lactoferrin are thought to concern inflammation and immunomodulation processes, including maturation of immature B and T cells. Lactoferrin accelerates T-cell maturation by inducing the expression of the CD4 surface marker. In this report, using the Jurkat T-cell line, we have shown that lactoferrin upregulates the expression of CD4 antigen through the activation of a transduction pathway. Using an anti-phosphotyrosine antibody, lactoferrin was demonstrated to induce a cascade of phosphorylation of numerous proteins on their tyrosine residues. This tyrosine-phosphorylation was transient, reaching maxima between 5 and 10 min. We also identified the mitogen-activated protein kinase (MAP kinase) which presented an enhanced catalytic activity, reaching a maximum at 10 min of incubation with lactoferrin. Moreover, the use of inhibitors such as genistein and PD98059, tyrosine kinases and MAP kinase kinase (or MEK) inhibitors respectively, allowed us to correlate the activation of MAP kinase with the upregulation of CD4 expression. Finally, using Lck-defective Jurkat cells, our results showed that the p56(lck) (Lck) kinase is necessary for MAP kinase activity and CD4 expression. This paper demonstrates that lactoferrin activates transduction pathway(s) in lymphoblastic T-cells, and that Lck and the Erk2 isoform of MAP kinase are implicated in the upregulation of CD4, induced by lactoferrin in these cells.

CD4 Antigens↗