CD4+ T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes
| Autor: | Jorge Kalil, R. Alencar, John Sidney, Alessandro Sette, Natalie Guida Muller, J. Hammer, Edecio Cunha-Neto, S. L. Moraes, Leda Fátima Jamal, Rodrigo Brindeiro |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Translational Studies medicine.medical_treatment T cell Molecular Sequence Data Immunology Epitopes T-Lymphocyte HIV Infections CD8-Positive T-Lymphocytes Biology Epitope Interleukin 21 HIV Protease Antigen medicine Humans Immunology and Allergy Cytotoxic T cell Protease inhibitor (pharmacology) Amino Acid Sequence Cells Cultured Protease HLA-DR Antigens Flow Cytometry Virology medicine.anatomical_structure Mutation HIV-1 Peptides Epitope Mapping CD8 Protein Binding |
| Zdroj: | Clinical and Experimental Immunology. 164:90-99 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.2011.04319.x |
| Popis: | Summary Human immunodeficiency virus (HIV)-1 protease is a known target of CD8+ T cell responses, but it is the only HIV-1 protein in which no fully characterized HIV-1 protease CD4 epitopes have been identified to date. We investigated the recognition of HIV-1 protease by CD4+ T cells from 75 HIV-1-infected, protease inhibitor (PI)-treated patients, using the 5,6-carboxyfluorescein diacetate succinimidyl ester-based proliferation assay. In order to identify putative promiscuous CD4+ T cell epitopes, we used the TEPITOPE algorithm to scan the sequence of the HXB2 HIV-1 protease. Protease regions 4–23, 45–64 and 73–95 were identified; 32 sequence variants of the mentioned regions, encoding frequent PI-induced mutations and polymorphisms, were also tested. On average, each peptide bound to five of 15 tested common human leucocyte antigen D-related (HLA-DR) molecules. More than 80% of the patients displayed CD4+ as well as CD8+ T cell recognition of at least one of the protease peptides. All 35 peptides were recognized. The response was not associated with particular HLA-DR or -DQ alleles. Our results thus indicate that protease is a frequent target of CD4+ along with CD8+ proliferative T cell responses by the majority of HIV-1-infected patients under PI therapy. The frequent finding of matching CD4+ and CD8+ T cell responses to the same peptides may indicate that CD4+ T cells provide cognate T cell help for the maintenance of long-living protease-specific functional CD8+ T cells. |
| Databáze: | OpenAIRE |
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