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Identification of novel consensus CD4 T-cell epitopes from clade B HIV-1 whole genome that are frequently recognized by HIV-1 infected patients

Fonseca, Simone Ga,b,c; Coutinho-Silva, Adrianaa,b,c; Fonseca, Luiz Augusto Ma,c; Segurado, Aluisio Cc,d; Moraes, Sandra La,c,e; Rodrigues, Hélciob; Hammer, Juergenf; Kallás, Esper Gc,g; Sidney, Johnh; Sette, Alessandroh; Kalil, Jorgea,b,c; Cunha-Neto, Edecioa,b,c

doi: 10.1097/01.aids.0000253353.48331.5f
Basic Science

Objective: To identify promiscuous and potentially protective human CD4 T-cell epitopes in most conserved regions within the protein-coding genome of HIV-1 clade B consensus sequence.

Design: We used the TEPITOPE algorithm to screen the most conserved regions of the whole genome of the HIV-1 subtype B consensus sequence to identify promiscuous human CD4 T-cell epitopes in HIV-1. The actual promiscuity of HLA binding of the 18 selected peptides was assessed by binding assays to nine prevalent HLA-DR molecules. Synthetic peptides were tested with interferon-γ ELISPOT assays on peripheral blood mononuclear cells (PBMC) from 38 HIV-1 infected patients and eight uninfected controls.

Results: Most peptides bound to multiple HLA-DR molecules. PBMC from 91% of chronically HIV-1 infected patients recognized at least one of the promiscuous peptides, while none of the healthy controls recognized peptides. All 18 peptides were recognized, and each peptide was recognized by at least 18% of patients; 44% of the patients recognized five or more peptides. This response was not associated to particular HLA-DR alleles. Similar responses were obtained in CD8 T-cell-depleted PBMC.

Conclusion: In silico prediction of promiscuous epitopes led to the identification of naturally immunodominant CD4 T-cell epitopes recognized by PBMC from a significant proportion of a genetically heterogeneous patient population exposed to HIV-1. This combination of CD4 T-cell epitopes – 11 of them not described before – may have the potential for inclusion in a vaccine against HIV-1, allowing the immunization of genetically distinct populations.

From the aDivision of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, Brazil

bHeart Institute (InCor),University of São Paulo School of Medicine, Brazil

cInstitute for Investigation in Immunology – Millenium Institutes, Brazil

dDepartment of Infectious Diseases, University of São Paulo School of Medicine, Brazil

eInstitute of Tropical Medicine, University of São Paulo, Brazil

fDepartment of Genomic and Information Sciences, Hoffmann-La Roche Inc., Nutley, New Jersey, USA

gDivision of Infectious and Parasitic Diseases, Federal University of São Paulo, Brazil

hLa Jolla Institute for Allergy and Immunology, San Diego, USA.

Received 19 June, 2006

Accepted 28 July, 2006

Correspondence to E. Cunha Neto, Laboratory of Immunology – Heart Institute (Incor), University of São Paulo School of Medicine, Av. Dr. Enéas de Carvalho Aguiar, 44, Bloco 2, 9 andar, São Paulo, SP, 05403-000, Brazil. Tel: +55 11 3069 5906; fax: +55 11 3069 5953; e-mail: edecunha@gmail.com

© 2006 Lippincott Williams & Wilkins, Inc.