title: Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection.
abstract: Virus-specific CD8(+) T cells are known to play an important role in the control of HIV infection. In this study we investigated whether there may be qualitative differences in the CD8(+) T cell response in HIV-1- and HIV-2-infected individuals that contribute to the relatively efficient control of the latter infection. A molecular comparison of global TCR heterogeneity showed a more oligoclonal pattern of CD8 cells in HIV-1- than HIV-2-infected patients. This was reflected in restricted and conserved TCR usage by CD8(+) T cells recognizing individual HLA-A2- and HLA-B57-restricted viral epitopes in HIV-1, with limited plasticity in their response to amino acid substitutions within these epitopes. The more diverse TCR usage observed for HIV-2-specific CD8(+) T cells was associated with an enhanced potential for CD8 expansion and IFN-gamma production on cross-recognition of variant epitopes. Our data suggest a mechanism that could account for any possible cross-protection that may be mediated by HIV-2-specific CD8(+) T cells against HIV-1 infection. Furthermore, they have implications for HIV vaccine development, demonstrating an association between a polyclonal, virus-specific CD8(+) T cell response and an enhanced capacity to tolerate substitutions within T cell epitopes.
authors.affiliation: Institute of Hepatology, University College London, London, United Kingdom.
authors.forename: A Ross
authors.initials: AR
authors.lastname: Lopes
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
authors.forename: Sehu
authors.initials: S
authors.lastname: Sabally
authors.forename: Abraham
authors.initials: A
authors.lastname: Alabi
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Jones
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
authors.forename: Anne
authors.initials: A
authors.lastname: De Groot
authors.forename: Phillipa
authors.initials: P
authors.lastname: Newton
authors.forename: R Monica
authors.initials: RM
authors.lastname: Lascar
authors.forename: Ian
authors.initials: I
authors.lastname: Williams
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Mala K
authors.initials: MK
authors.lastname: Maini
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000276:immunology; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015683:Gene Products, gag / Q000276:immunology / Q000378:metabolism; D015329:Gene Rearrangement, T-Lymphocyte / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D015498:HIV-2 / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta