AEGiS-11IAC: Strain-specific cytotoxic T lymphocyte responses directed against human immunodeficiency virus type 1 env.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Strain-specific cytotoxic T lymphocyte responses directed against human immunodeficiency virus type 1 env.

Int Conf AIDS 1996 Jul 7-12; 11:223 (abstract no. Tu.A.284)
Bollinger RC, Siliciano RF, Lubaki N, Dhruva B, Ray S; Johns Hopkins University, Baltimore, MD. Fax: 410-955-7889. E-mail: RCB@welchlink.welch.jhu.edu.

Rationale: Assays of HIV-1 env-specific, cytotoxic T lymphocyte (CTL) activity typically measure responses directed against standard laboratory strains of HIV-1, such as IIIB or MN. Most candidate HIV vaccines are also based on the same strains. Given that a single amino acid change can abrogate CTL recognition and the natural variants of HIV-1 env have great genetic variability, the specific role of env-specific CTL is difficult to assess using standard HIV-1 strains as target antigens.

OBJECTIVE: To compare and characterize the CTL response directed against HIV-1 env from standard laboratory strains and autologous viral strains from HIV-1-infected individuals.

METHODS: The gp120 coding sequence was amplified from proviral DNA isolated from 2 individuals with HIV-1 infection. The gp120 genes were cloned and expressed in vaccinia. CTL activity against autologous env was measured in direct and unstimulated PBMC. HIV-1 env-specific, CTL clones were isolated and characterized.

RESULTS: CTL activity directed against autologous env was greater than activity directed against IIIB env in both subjects. This strain-specific CTL activity was mediated by CD8+ T cells and was much more efficiently inhibited by the use of autologous gp120 expressing cold targets, then with IIIB gp120 expressing cold targets. Eight env-specific CTL clones, utilizing 3 different HLA class I alleles, were isolated and characterizedfrom one subject. Five clones recognized autologous, IIIB, MN and RF HIV-1 env. Three clones were strain-specific, including 1 clone that only recognized autologous and MN env. The use of vaccinia constructs expressing truncated HIV-1 env localized the CTL epitopes of these clones to 3 different regions of env and determination of the minimal epitopes of these CTL clones in ongoing.

CONCLUSIONS: Some HIV-1 infected individuals have strain-specific CTL activity. Standard assays do not full detect or characterize env-specific CTL activity. An effective CTL response may require a broad, polyclonal response directed at conserved and variable (strain-specific) epitopes. Characterization of strain-specific CTL activity may have important implications for understanding HIV pathogenesis and vaccine design.

Keywords: AEGIS, T-Lymphocytes, Cytotoxic, HIV-1, HIV Infections, AIDS Vaccines, Antigens, CD8, Epitopes, HIV-1 Reverse Transcriptase, Resin Cements, Direct, Human, ICA11

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TuA284