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58 Clustered T-Helper Determinants in the HIV Envelope Protein
T. Lockey*, S. Surman, K. S. Slobod, B. Jones, J. Riberdy, B. Brown, A. Zirkel, S. White, P. Doherty, and J. L. Hurwitz
St. Jude Children’s Res. Hosp., Memphis, TN, USA
A comprehensive analysis was performed to define T-helper (Th) epitopes on the human immunodeficiency virus (HIV) envelope protein. Mice were grouped to receive 1 of 2 HIV envelope vaccines (representing either a clade B or clade D HIV isolate), after which more than 100 unique Th hybridomas were prepared. Overlapping peptides were synthesized to span the envelope proteins and were used to identify the epitope recognized by each T-cell hybridoma. T-cell receptors (TCR) were also characterized with a panel of Valpha-?and Vbeta-specific antibodies to identify unique T-cell clonal populations. Results revealed a striking positional effect on Th epitope selection. Epitopes appeared within only 4 regions of the HIV envelope protein. These hotspots were relatively short sequences (of approximately 20(80 amino acids in length) within regions of heavy glycosylation. Regions lacking glycosylation harbored no Th determinants. Epitope analysis in the context of the gp120 crystal structure showed a pattern of uniform distribution to 1 exposed face of the envelope protein. A likely explanation for these results is that the physical location of the peptide within the native protein leads to differential antigen processing and consequent epitope selection.
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