Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection.
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.
Lopes
A Ross
AR
Institute of Hepatology, University College London, London, United Kingdom.
Jaye
Assan
A
Dorrell
Lucy
L
Sabally
Sehu
S
Alabi
Abraham
A
Jones
Nicola A
NA
Flower
Darren R
DR
De Groot
Anne
A
Newton
Phillipa
P
Lascar
R Monica
RM
Williams
Ian
I
Whittle
Hilton
H
Bertoletti
Antonio
A
Borrow
Persephone
P
Maini
Mala K
MK
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
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta