AEGiS-14IAC: Cytotoxic T lymphocyte (CTL) responses restricted by HLA-B7, -B42 and -B81 in African HIV-1 positive women and their babies.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Cytotoxic T lymphocyte (CTL) responses restricted by HLA-B7, -B42 and -B81 in African HIV-1 positive women and their babies.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no.. TuOrA1184)

Mngqundaniso N
South Africa

BACKGROUND: The host immune response plays a critical role in defining the viral set point in persons infected with HIV-1. Cytotoxic T-lymphocytes are a major mediator of antiviral activity. The way the CTLs control viraemia depend on the HLA type of the individual. Some studies have shown that are of great advantage than others. An effective HIV vaccine should induce strong antiviral CTL activity. Therefore, understanding the viral targets of this response is important in order to facilitate the design and testing of candidate vaccines. Few HIV-1 immunology studies to date have focused on populations most affected by the HIV-1 epidemic.

METHODS: Ante-natal attendees with HIV-1 clade C virus from the Cato Manor clinic in Durban, south Africa were screened for CTL responses to the Gag (p17 and p24), RT, Nef, Tat and Rev gene products using overlapping peptide sets in an enzyme linked immunospot assay (ELISPOT). Intracellular IFN-γ staining (ICS) of cells which were stimulated with particular peptide allowed the CD8 or CD4 dependence of the responding cells to be determined by flow cytometry. In addition the peptide MHC class I tetramer assay was used to determine the specificity of a single CTL response. HLA class I subtypes were determined by SSP-PCR and viral load using the Roche Amplicor kit.

RESULTS: The immunodominant region targeted was the gag region particularly an epitope in p24 gag (TPQDLNTML), (TL9). This was due to HLA class I molecules B42, B7 and B81 which are expressed in 40-45% of the Zulu/Xhosa population in Durban. This specific TL9 CTL epitope response was consistent over time in the same patients who harboured the B42 allele.

CONCLUSION: HLA-B42 class I molecule is associated with control of clade C HIV infection in African Zulu/Xhosa population. p24 gag TL9 CTL epitope response is stable over time and may be a good candidate to include in vaccine design.

Keywords: AEGIS, HIV-1, T-Lymphocytes, Cytotoxic, HLA-B7 Antigen, HIV Infections, AIDS Vaccines, Epitopes, Immunodominant Epitopes, African Continental Ancestry Group, HLA Antigens, Gene Products, rev, South Africa, Infant, Human, Female, immunology

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TuOrA1184