High degree of inter-clade cross-reactivity of HIV-1-specific T cell responses at the single peptide level.
OBJECTIVE
To determine HIV-1-specific T cell responses in clade B infected individuals recognizing the clade A, B and C consensus sequences in order to assess the degree of inter-clade cross-reactivity of these immune responses at the single epitope level.


METHODS
HIV-1-specific T cell responses were assessed cross-sectionally in 27 chronically HIV-1-infected individuals from a population infected mainly with clade B viral strains, using an interferon-gamma Elispot assay with a total of 1230 overlapping peptides spanning the entire amino acid sequence of the clade A, B and C 2001 consensus sequences.


RESULTS
No significant difference was observed between the total magnitude or breadth of T cell responses recognizing either the clade A, B or C consensus sequences. However, at the single peptide level, 194 T cell responses were identified that recognized only one of the three different clade-specific peptide variants (A: B: C, 34: 105: 55), 125 T cell responses recognized two of the three peptide variants (AB: AC: BC, 71: 15: 39) and 166 T cell responses (34%) were cross-reactive with all three different peptide variants. Peptides recognized in all three consensus sequence variants had a significantly lower entropy (P < 0.0001) and a significantly higher inter-clade homology (P < 0.0001).


CONCLUSIONS
Viral epitopes within regions of low HIV-1 clade B diversity and high inter-clade homology can be recognized in the clade A, B and C variants and indicate a wide degree of cross-isolate and cross-clade recognition by HIV-1-specific T cells. These regions may therefore be of particular relevance for the design of HIV-1 vaccines.
Yu
Xu G
XG
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA. xyu@partners.org
Lichterfeld
Mathias
M
Perkins
Beth
B
Kalife
Elizabeth
E
Mui
Stanley
S
Chen
Jianping
J
Cheng
Michael
M
Kang
Wenzhen
W
Alter
Galit
G
Brander
Christian
C
Walker
Bruce D
BD
Altfeld
Marcus
M
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016384:Consensus Sequence / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008875:Middle Aged
D018984:Epitopes, T-Lymphocyte