Characterization of an HLA-C-restricted CTL response in chronic HIV infection.
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.
Makadzange
Azure T
AT
Medical Research Council, Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Gillespie
Geraldine
G
Dong
Tao
T
Kiama
Peter
P
Bwayo
Job
J
Kimani
Joshua
J
Plummer
Frank
F
Easterbrook
Philippa
P
Rowland-Jones
Sarah L
SL
D044383:Black People / Q000235:genetics; D018106:CD28 Antigens / Q000032:analysis; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D015331:Cohort Studies; D005434:Flow Cytometry; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000208:ethnology / Q000276:immunology*; D015497:HIV-1; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D044465:White People / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000502:physiology
D018106:CD28 Antigens; D015488:HIV Antigens; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D016056:Immunodominant Epitopes; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D007371:Interferon-gamma