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Characterization of an HLA-C-restricted CTL response in chronic HIV infection.

Abstract
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.
AuthorsAzure T Makadzange, Geraldine Gillespie, Tao Dong, Peter Kiama, Job Bwayo, Joshua Kimani, Frank Plummer, Philippa Easterbrook, Sarah L Rowland-Jones
JournalEuropean journal of immunology (Eur J Immunol) Vol. 40 Issue 4 Pg. 1036-41 (Apr 2010) ISSN: 1521-4141 [Electronic] Germany
PMID20104487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CD28 Antigens
  • HIV Antigens
  • HLA-C Antigens
  • HLA-C*04 antigen
  • Immunodominant Epitopes
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • Interferon-gamma
Topics
  • Black People (genetics)
  • CD28 Antigens (analysis)
  • CD4 Lymphocyte Count
  • Chronic Disease
  • Cohort Studies
  • Flow Cytometry
  • HIV Antigens (immunology)
  • HIV Infections (ethnology, immunology)
  • HIV-1
  • HLA-C Antigens (genetics, immunology)
  • Humans
  • Immunodominant Epitopes (immunology)
  • Immunologic Memory (immunology)
  • Immunophenotyping
  • Interferon-gamma (metabolism)
  • T-Lymphocyte Subsets (immunology)
  • T-Lymphocytes, Cytotoxic (immunology)
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 (analysis)
  • White People (genetics)
  • nef Gene Products, Human Immunodeficiency Virus (physiology)

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