CTLs from lymphoid organs recognize an optimal HLA-A2-restricted and HLA-B52-restricted nonapeptide and several epitopes in the C-terminal region of HIV-1 Nef
| Autor: | F Hadida, G Haas, N Zimmermann, A Hosmalin, R Spohn, A Samri, G Jung, P Debre, B Autran |
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| Rok vydání: | 1995 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 154:4174-4186 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.154.8.4174 |
| Popis: | In a previous analysis of HIV-1-specific CTLs in lymphoid organs from HIV-seropositive patients, we reported high frequencies of in vivo differentiated CTLs directed against two immunodominant regions in the central and in the C-terminal part of the HIV-1 Nef protein. The present study analyzes the epitopes recognized by CTLs in the carboxyl terminus of Nef (amino acids 182-205). In addition to several epitopes that are recognized in association with different HLA molecules (A1, A2, A25(10), B35, B52), we defined an optimal nonapeptide (190-198). This nonapeptide was recognized by CTLs down to nanomolar concentrations in the context of at least two HLA molecules, HLA-B52 and HLA-A2, including three HLA-A2 subtypes: HLA-A2.1, -A2.2, and -A2.4. We also determined the relative frequencies of effector CTLs directed against peptide 190-198 to be as high as 10(-4), as opposed to lower frequencies ranging between 5 x 10(-5) and 5 x 10(-6) observed for the other peptides recognized in the same region, thus confirming the optimal presentation of this nonapeptide in vivo. Molecular modeling of the interactions between HLA-A2.1 and Nef peptide 190-198 suggests the formation of a stable complex and allowed us to study sequence motifs that are important for the binding of the HIV-1 peptide in the pockets of the HLA-A2.1 molecule. |
| Databáze: | OpenAIRE |
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