title: Shaping T cell - B cell collaboration in the response to human immunodeficiency virus type 1 envelope glycoprotein gp120 by peptide priming.
abstract: Prime-boost vaccination regimes have shown promise for obtaining protective immunity to HIV. Poorly understood mechanisms of cellular immunity could be responsible for improved humoral responses. Although CD4+ T-cell help promotes B-cell development, the relationship of CD4+ T-cell specificity to antibody specificity has not been systematically investigated. Here, protein and peptide-specific immune responses to HIV-1 gp120 were characterized in groups of ten mucosally immunized BALB/c mice. Protein and peptide reactivity of serum antibody was tested for correlation with cytokine secretion by splenocytes restimulated with individual gp120 peptides. Antibody titer for gp120 correlated poorly with the peptide-stimulated T-cell response. In contrast, titers for conformational epitopes, measured as crossreactivity or CD4-blocking, correlated with average interleukin-2 and interleukin-5 production in response to gp120 peptides. Antibodies specific for conformational epitopes and individual gp120 peptides typically correlated with T-cell responses to several peptides. In order to modify the specificity of immune responses, animals were primed with a gp120 peptide prior to immunization with protein. Priming induced distinct peptide-specific correlations of antibodies and T-cells. The majority of correlated antibodies were specific for the primed peptides or other peptides nearby in the gp120 sequence. These studies suggest that the dominant B-cell subsets recruit the dominant T-cell subsets and that T-B collaborations can be shaped by epitope-specific priming.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: N Kalaya
authors.initials: NK
authors.lastname: Steede
authors.forename: Blake J
authors.initials: BJ
authors.lastname: Rust
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Hossain
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Freytag
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Landry
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D010455:Peptides