AEGiS-15IAC: Identification of novel CD4 T cells promiscuous epitopes from whole protein sequence of clade b HIV-1 consensus.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Identification of novel CD4 T cells promiscuous epitopes from whole protein sequence of clade b HIV-1 consensus.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrA1005)

Fonseca SG, Silva AC, Fonseca LA, Leite O, Gutierrez E, Santos S, Segurado A, Iwai LK, Hammer J, Sidney J, Sette A, Kalil J, Cunha-Neto E
Heart Institute, Division of Clinical Immunology and Allergy, School of Medicine, Sao Paulo, Brazil

BACKGROUND: The control of viral load of immunocompetent HIV+ patients is associated with an effective anti-HIV CD4+ T cell response. The aim of this work is to identify a set of HIV derived-peptides that bind promiscuously to several different HLA molecules, covering close to 100% of the genetically diverse human population.

METHODS: We searched the whole HIV-1 clade B consensus protein-coding genome for promiscuous epitopes with the TEPITOPE algorithm and tested them in PBMC from Long Term Non-Progressor (LTNP) patients using IFN-g ELISPOT assay. TEPITOPE algorithm, that predicts binding to 25 distinct HLA-DR molecules, allows for the potential selection of peptides binding with high affinity to HLA molecules.

RESULTS: We identified twenty 12-20-mer peptides from env, gag, pol, vpu, vpr, rev, vif, vpu, predicted to bind to at least 16/25 HLA-DR molecules; each HLA molecule was predicted to bind to at least 6/20 peptides, allowing for variation of T cell recognition. 60% of these peptides were novel epitopes. Seven out of 20 peptides were recognized by all two LTNP individuals tested (>20 spots/106 cells) and 4 from these 7 peptides were identified as novel CD4+ T cell epitopes derived from gag, pol, env and vif proteins. HLA-DR binding assay showed that all 7 peptides bound to at least 6 HLA-DR out of 9 molecules tested, confirming their promiscuity. Conclusion Our results suggest that our set of selected peptides, including novel CD4+ T cell epitopes could be an attractive tool to evaluate the immune response of HIV+ patients and might allow their use in vaccine trials. Supported by FAPESP, CNPq - sfonseca@usp.br

Keywords: AEGIS, HIV-1, Epitopes, T-Lymphocyte, Antigens, CD4, Amino Acid Sequence, Gene Products, vif, HIV Envelope Protein gp120, HLA-DR Antigens, HIV Infections, HIV, Peptides, HIV Antigens, Epitopes, Acquired Immunodeficiency Syndrome, Genes, gag, Genes, env, HIV Seropositivity, Humans, immunology, genetics

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MoOrA1005