HIV p24-specific helper T cell clones from immunized primates recognize highly conserved regions of HIV-1
| Autor: | Kingston Mills, Pa, Kitchin, Bp, Mahon, Al, Barnard, Se, Adams, Sm, Kingsman, Aj, Kingsman |
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| Předmět: |
CD4-Positive T-Lymphocytes
HIV Antigens Viral Core Proteins Molecular Sequence Data HIV Core Protein p24 Gene Products gag T-Lymphocytes Helper-Inducer Clone Cells Major Histocompatibility Complex Epitopes Macaca fascicularis Structure-Activity Relationship HIV-2 HIV-1 Animals Simian Immunodeficiency Virus Amino Acid Sequence |
| Zdroj: | Europe PubMed Central |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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