HIV p24-specific helper T cell clones from immunized primates recognize highly conserved regions of HIV-1.
We have investigated Th cell recognition of the HIV core protein p24 by using CD4+ T cell clones derived from cynomolgus macaques immunized with hybrid HIV p24: Ty virus-like particles (VLP). T cell lines from two immunized animals responded to p24: Ty-VLP, control Ty-VLP, purified p24, and whole inactivated HIV, indicating the presence of T cells specific for p24 as well as the Ty carrier protein. The HIV determinants recognized by the T cell lines were identified by using a series of overlapping peptides synthesized according to the sequence of p24. Both T cell lines recognized peptide 11 (amino acids 235-249) and peptide 14 (amino acids 265-279). In addition, one T cell line also responded to peptide 9 (amino acids 215-229). Definitive identification of two T cell epitopes on p24 was confirmed at the clonal level: from a total of four T cell clones generated from one of the T cell lines, two respond specifically to peptide 11 and two to peptide 14. The T cell clones were CD4+ and MHC class II-restricted and secreted IL-2 in response to stimulation with purified p24, inactivated HIV or a single synthetic peptide. The specificity of the Th clones for variant peptides demonstrated cross-reactivity with two simian immunodeficiency virus isolates, but only limited responses to HIV-2 sequences. However, the Th cell epitopes identified on p24 are highly conserved between 12 HIV-1 isolates and were recognized by both of the immunized primates. These sequences may therefore be useful for priming a broadly reactive immune response to HIV-1.
Mills
K H
KH
National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts, UK.
Kitchin
P A
PA
Mahon
B P
BP
Barnard
A L
AL
Adams
S E
SE
Kingsman
S M
SM
Kingsman
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D000939:Epitopes; D015683:Gene Products, gag / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology; D008252:Macaca fascicularis; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
D000939:Epitopes; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D014758:Viral Core Proteins