Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover.
The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)-B27 patients. To understand further the nature of CD8+ T cell-mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27-restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10-specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.
Almeida
Jorge R
JR
Cellular Immunology Laboratory, U543, Institut National de la Santé et de la Recherche Médicale, Avenir Group, 75013 Paris, France.
Price
David A
DA
Papagno
Laura
L
Arkoub
Zaïna Aït
ZA
Sauce
Delphine
D
Bornstein
Ethan
E
Asher
Tedi E
TE
Samri
Assia
A
Schnuriger
Aurélie
A
Theodorou
Ioannis
I
Costagliola
Dominique
D
Rouzioux
Christine
C
Agut
Henri
H
Marcelin
Anne-Geneviève
AG
Douek
Daniel
D
Autran
Brigitte
B
Appay
Victor
V
D000595:Amino Acid Sequence; D018959:CD57 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D016922:Cellular Senescence; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000502:physiology*; D015796:HLA-B27 Antigen / Q000737:chemistry / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D014779:Virus Replication
D018959:CD57 Antigens; D015683:Gene Products, gag; D015796:HLA-B27 Antigen