Trocha AK, Brown NV, Frahm N, Adams S, Marincola F, Walker BD, Brander C; International Conference on AIDS (15th : 2004 : Bangkok, Thailand).

Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. ThOrA1393.

Mass. General Hospital and Howard Hughes Medical Institute, Boston, United States

Background: HIV-1 derived CTL epitopes have been shown to be promiscuously presented by multiple HLA class I alleles. Epitopes that are shared by HLA-A, -B and -C alleles could be employed to assess the effect that Nef-mediated HLA classI down-regulation has on the ability of CTL to inhibit viral replication. Methods: In vitro CTL mediated inhibition of viral replication was used to test the ability of different CTL clones to inhibit the replication of wild-type and Nef deleted viruses. The CTL clones/lines were all specific for the same gp41 epitope and were restricted either by HLA-Cw3, -Cw15 and -B58. Peptide titrations of the targeted peptide were performed to assess the functional avidity of the different CTL clones. Results: The gp41 RL9 epitope was not cross-recognized between HLA-Cw3, -Cw15 and -B58, and titration curves using serially truncated peptides confirmed RAIEAQQHL as the optimal epitope for all 3 alleles. Our data demonstrate that HLA-Cw15 restricted CTL clones can efficiently inhibit in vitro viral replication. While Nef did not appear to interfere with the antiviral effect of the Cw15 restricted CTL clone, suppression of viral replication by the Cw3 restricted CTL clone was less effective in the presence of Nef. Experiments using the RL9 specific, HLA-B58 restricted lines are in progress. Conclusions: Since HLA-B58 but not HLA-Cw3 or -Cw15 are associated with slow HIV disease progression, the present data suggest that in vivo, factors other than the HLA specific susceptibility to Nef mediated down-regulation are contributing to the effectiveness of CTL responses. The availability of epitopes shared between HLA alleles differentially associated with slow or fast HIV disease progression provides the opportunity to identify these factors and assess their relative contribution to control of HIV in vitro and in vivo.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Alleles
• Epitopes
• HIV
• HIV Antigens
• HIV Infections
• HIV Seropositivity
• HIV-1
• HLA Antigens
• HLA-C Antigens
• HLA-Cw15 protein, human
• HLA-Cw3
• In Vitro
• T-Lymphocytes, Cytotoxic
• genetics
• immunology

Other ID:

• GWAIDS0036400

UI: 102280616

From Meeting Abstracts