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


METHODS
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-gamma 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.


CONCLUSIONS
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.
Fonseca
Simone G
SG
Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, Brazil.
Coutinho-Silva
Adriana
A
Fonseca
Luiz Augusto M
LA
Segurado
Aluisio C
AC
Moraes
Sandra L
SL
Rodrigues
Hélcio
H
Hammer
Juergen
J
Kallás
Esper G
EG
Sidney
John
J
Sette
Alessandro
A
Kalil
Jorge
J
Cunha-Neto
Edecio
E
D000328:Adult; D000368:Aged; D000465:Algorithms; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016384:Consensus Sequence; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology*; D005260:Female; D016679:Genome, Viral / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000939:Epitopes; D006684:HLA-DR Antigens; D010455:Peptides; D014764:Viral Proteins; D007371:Interferon-gamma