Norris P, Nguyen T, Walker B, Rosenberg E; International Conference on AIDS.
Int Conf AIDS. 2000 Jul 9-14; 13: abstract no. MoPpA1001.
P. Norris, Massachusetts General Hospital, Massachusetts General Hospital, 55 Fruit Street, GRJ 504, Boston, MA 02114, United States, Tel.: +1 6127 724 7514, Fax: +1 617 724 5890, E-mail: pnorris@partners.org
Background: Recent studies have demonstrated that HIV-1-specific T helper cell responses are inversely associated with control of viral replication in chronically infected persons. We studied one chronically HIV infected individual with long-term nonprogressive infection who has maintained a low to undetectable viral load without antiviral therapy. Methods: We identified and mapped p24 specific T helper cell epitopes and generated an HIV-specific T helper cell clone directed against the immunodominant epitope. The clone was characterized by performing proliferation, ELISPOT, and cytotoxicity assays. Results: Using synthetically derived overlapping peptides spanning the entire p24 protein, we were able to map the minimum peptide required to induce an immune response in a 3H-thymidine-uptake proliferation assay, and the same epitope was also the minimum epitope in an Elispot assay for IFN-gamma. Using truncations of the targeted peptide, we found the minimal peptide VHAGPIAPG induced a stimulation index of 121 and a delta-CPM of 5062. With a 51Cr-release assay we found that the clone effected up to a 70% killing of autologous B-LCL expressing the minimal epitope at an effector to target cell ratio of 10:1. Conclusions: These results indicate that the same 9 amino acid epitope in p24 is able to stimulate proliferation of T helper cells and to serve as the target epitope for a CD4-mediated cytolytic response. This work supported by a NIH Training grant and an unrestricted grant from Cable Positive.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Antigens, CD4
- CASP4 protein, human
- CD4-Positive T-Lymphocytes
- Caspases
- Epitopes
- HIV Infections
- HIV Seropositivity
- HIV-1
- T-Lymphocytes
- T-Lymphocytes, Helper-Inducer
- Viral Load
- Viremia
- immunology
Other ID:
UI: 102237526
From Meeting Abstracts