Dendritic cell vaccine models allow for identification of novel T cell epitopes in HIV-1 nef.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Dendritic cell vaccine models allow for identification of novel T cell epitopes in HIV-1 nef.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:47. Unique Identifier : AIDSLINE MED/97927031
Wilson CC; Rinaldo CR; Tueting T; Martin D; Farhood H; Lotze MT; Storkus WJ; University of Pittsburgh Medical Center, Pittsburgh, PA. Fax: 412); 624-1172.

Abstract: An in vitro vaccine model for HIV-1 was developed using cultured DC as stimulators and naive T cells from HIV-1 seronegative donors as responders. DC cultured from nonadherent PBMC in GM-CSF and IL-4 for 5-10 days were pulsed with recombinant Nef antigen or were transfected with the HIV-1 nef gene. Human IL-12 and IFN-alpha were added to DC during priming, or DC were co-transfected with cDNA encoding these cytokines and Nef. Responder T cells were primed in vitro, re-stimulated on a weekly basis, and tested for the ability to recognize Nef-expressing targets. Following priming with DC + Nef protein, proliferative responses to rNef could be seen as early as the third round of stimulation. Responses were dose-dependent with S.I. ranging from 2.2 to 25, and were blocked with anti-MHC II mAb. DC pulsed with Nef + liposomes led to the induction of the strongest MHC II-restricted responses in some cases. CTL against autologous BCL pulsed with Nef peptides were generated following induction with DC-Nef protein, and responses were enhanced by the addition of rIL-12 or rIFN-alpha during priming. DC transfected with the nef gene were potent inducers of Nef-specific CTL, and a novel epitope in Nef restricted by HLA-B7 was identified. Different patterns of nef peptide recognition were seen when Th1-associated cytokines were co-transfected with the nef gene. This in vitro system may be useful in identifying novel epitopes as vaccine targets and evaluating effects of cytokines on T cell induction. Successful approaches may be translated into clinical DC-based vaccines for HIV-1.

Keywords: *AIDS Vaccines/IMMUNOLOGY *Dendritic Cells/IMMUNOLOGY *Epitopes/ANALYSIS *Gene Products, nef/IMMUNOLOGY *HIV-1/IMMUNOLOGY
971130
M97B1190

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1997. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .