537-M. Sequential Broadening of HIV-1-Specific CTL Responses during Supervised Treatment Interruption in Treated Acute Infection

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Session 72 Poster Session
Treatment Interruption
Session Time: 4:30-6:30 pm
Room 4E-F

537-M.

Sequential Broadening of HIV-1-Specific CTL Responses during Supervised Treatment Interruption in Treated Acute Infection
X. Yu*¹, M. M. Addo¹, C. Fitzpatrick , P. Lee, D. Strick, P. Goulder, E. Rosenberg², B. Walker³, and M. Altfeld¹
¹Partners AIDS Res. Ctr.; ²Massachussetts Gen. Hosp.; and ³Harvard Med. Sch., Boston, MA

Background: Increasing evidence indicates that HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL) and CD4+ T helper cells play a critical role in the control of viral replication in HIV-1 infection. However, the entire breadth and magnitude of HIV-1-specific CTL responses that can be reached in an infected individual is not known as epitope-specific CTL responses have never been assessed fully comprehensively in a single individual.
Methods: We describe the first comprehensive characterization of HIV-1-specific CTL responses in an infected individual, using 505 overlapping peptides spanning the entire expressed HIV-1 sequence, in an IFN-gamma assay. All optimal epitopes targeted by CTL of the study subject were defined after isolation of epitope-specific CTL lines. Longitudinal study was done using samples from 11 different time-points starting from acute infection to address the impact of supervised treatment interruption (STI) on CTL responses.
Results: Virus-specific CD8+ T-cell responses were directed against a total of 25 different regions of the virus, containing 27 optimal CTL epitopes. These epitopes include 13 novel epitopes that are described for the first time in this individual. Up to 16 different CTL epitopes were restricted by a single HLA class I molecule (HLA-A3). Longitudinal studies starting at the time of acute infection demonstrated that only 2 epitopes were targeted during acute infection, but CTL responses broadened significantly during supervised treatment interruption.
Conclusions: These studies demonstrate that HIV-1-specific CTL responses can be enhanced to a so far unexpected and unprecedented breadth by immunotherapeutic interventions in an infected individual.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections