6th International AIDS Conference San Francisco, California, USA — June 20-23, 1990

Int Conf AIDS 1990 Jun 20-23; 6:314 (abstract no. 1000)
Repke H, Shin J, Barber E, Rudd C, Helland D, Haseltine W; Dana Farber Cancer Institute, Boston, MA, USA

OBJECTIVE: Do gangliosides induce a new mechanism of CD4- down modulation at human T-cells?

METHODS: 1) Quantitative measurement CD4 down modulation and HIV-infection with and without site directed mutagenesis within the cytoplasmic chain of CD4. 2) Detection of selective protein phosphorylation by immunoprecipitation. 3) Effect of gangliosides on artificial Ca(++)-channels and transglutaminase.

RESULTS: Different pure gangliosides associate within 30 sec. with human T-cells as indicated by the newly discovered inhibitory effect on Ca(++)-channels. However, the complete down modulation of CD4 requires one hour and is accompanied with an inhibition of HIV-1 infection. Site directed mutagenesis proves that the process is independent of CD4-phosphorylation and not attributable to a blockade of extracellular binding sites. Gangliosides induce the dissociation of the tyrosine protein kinase p56(LCK) from CD4. For the first time, evidence is provided that CD4 is associated with one target of the p56(LCK), i.e. CD3( ). Removal of the glutamine containing cytoplasmic sequence and transglutaminase inhibitors inhibit the ganglioside effect completely.

CONCLUSION: Gangliosides act on a basically new mechanism of complete CD4-internalization which involves the CD4- associated p56(LCK) and covalent CD4- cross linking by a transglutaminase.

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