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60 Allocation of Helper T-Cell Epitope Immunodominance According to Three-Dimensional Structure in the Human Immunodeficiency Virus Type I Envelope Glycoprotein gp120
S. J. Landry*, G. Dai, and N. K. Steede
Tulane Univ. Hlth. Sci. Ctr., New Orleans, LA, US
Background:Promiscuously immunodominant helper T-cell epitopes in the HIV envelope glycoprotein gp120 could be important in the development of broadly protective immunity, but the underlying mechanisms of immunodominance and promiscuity remain poorly defined.
Methods:In this study, gp120 helper T-cell epitopes were systematically mapped in CBA/J and BALB/c mice by restimulation assays using a set of overlapping peptides spanning the entire sequence of the gp120 encoded by HIV strain 89.6. The results were analyzed in the context of the HIV gp120 structure determined by x-ray crystallography.
Results:One major finding was that all of the promiscuously immunodominant gp120 sequences are located in the “outer” domain, whereas the uniquely immunodominant sequences are in the “inner” domain. Further analyses indicated that epitope immunogenicity in the outer domain correlates with structural disorder in adjacent N-terminal segments, as indicated by crystallographic B-factors or sequence divergence. In contrast, the correlation was poor when the analysis encompassed the entire gp120 sequence or was restricted to only the inner domain.
Conclusions:These findings indicate that 3-dimensional structure influences the processing and presentation of gp120 and thus helper T-cell epitope immunogenicity.
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