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HIV-specific CTL play an important role in the host control of HIV infection. HIV-nef may facilitate escape of HIV-infected cells from CTL recognition by selectively downregulating the expression of HLA-A and HLA-B molecules, while surface expression of HLA-C is unaffected. The HLA-C-restricted CTL responses have previously been largely ignored and poorly characterized. We examined the frequency, function, and phenotype of HLA-C-restricted CTL in ten antiretroviral therapy-naïve Caucasian and African individuals with chronic HIV-1 infection (for at least 8 years; CD4 cell counts in the range of 50-350) who carried the HLA-Cw04 allele. HLA-Cw04-restricted CTL that recognize a conserved epitope within HIV-1 envelope (aa 375-383 SF9) were analyzed using IFN-gamma ELISPOT assays and phenotypic analysis was carried out by flow cytometry. HLA-C-restricted CTL play an important role in the HIV-specific response, and can account for as much as 54% of the total response. HLA-C-restricted CTL are functionally and phenotypically identical to HLA-A- and HLA-B-restricted CTL. HLA-C-restricted CTL in chronic HIV infection are memory cells of an intermediate phenotype, characterized by high CD27 and low CD28 expression and lack of perforin production.

Original publication




Journal article


Eur J Immunol

Publication Date





1036 - 1041


African Continental Ancestry Group, CD28 Antigens, CD4 Lymphocyte Count, Chronic Disease, Cohort Studies, European Continental Ancestry Group, Flow Cytometry, HIV Antigens, HIV Infections, HIV-1, HLA-C Antigens, Humans, Immunodominant Epitopes, Immunologic Memory, Immunophenotyping, Interferon-gamma, T-Lymphocyte Subsets, T-Lymphocytes, Cytotoxic, Tumor Necrosis Factor Receptor Superfamily, Member 7, nef Gene Products, Human Immunodeficiency Virus