Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. Export

@article{citeulike:6021842, abstract = {Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most affected by the epidemic. In this study, we examined the CD8(+)-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8(+)-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88\% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90\% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8(+)-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting class I molecules. The present study thus identifies factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations.}, author = {Frahm, Nicole and Korber, B. T. and Adams, C. M. and Szinger, J. J. and Draenert, R. and Addo, M. M. and Feeney, M. E. and Yusim, K. and Sango, K. and Brown, N. V. and SenGupta, D. and Piechocka-Trocha, A. and Simonis, T. and Marincola, F. M. and Wurcel, A. G. and Stone, D. R. and Russell, C. J. and Adolf, P. and Cohen, D. and Roach, T. and StJohn, A. and Khatri, A. and Davis, K. and Mullins, J. and Goulder, P. J. and Walker, B. D. and Brander, C.}, citeulike-article-id = {6021842}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/14963115}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=14963115}, issn = {0022-538X}, journal = {Journal of virology}, keywords = {elispot\_assay, hiv, hla\_class}, month = {March}, number = {5}, pages = {2187--2200}, posted-at = {2009-10-28 19:04:34}, priority = {2}, title = {Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/14963115}, volume = {78}, year = {2004} }

TY - JOUR ID - citeulike:6021842 L3 - citeulike-article-id:6021842 N2 - Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most affected by the epidemic. In this study, we examined the CD8(+)-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8(+)-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8(+)-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting class I molecules. The present study thus identifies factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations. IS - 5 JF - Journal of virology SN - 0022-538X EP - 2200 TI - Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. VL - 78 SP - 2187 KW - elispot_assay KW - hiv KW - hla_class AU - Frahm, Nicole AU - Korber, BT AU - Adams, CM AU - Szinger, JJ AU - Draenert, R AU - Addo, MM AU - Feeney, ME AU - Yusim, K AU - Sango, K AU - Brown, NV AU - SenGupta, D AU - Piechocka-Trocha, A AU - Simonis, T AU - Marincola, FM AU - Wurcel, AG AU - Stone, DR AU - Russell, CJ AU - Adolf, P AU - Cohen, D AU - Roach, T AU - StJohn, A AU - Khatri, A AU - Davis, K AU - Mullins, J AU - Goulder, PJ AU - Walker, BD AU - Brander, C PY - 2004/03// UR - http://view.ncbi.nlm.nih.gov/pubmed/14963115 ER -