A V3 loop haptenic peptide sequence, when tandemly repeated, enhances immunogenicity by facilitating helper T-cell responses to a covalently linked carrier protein.
Subunit immunogens containing tandemly repeated copies of T- and B-cell epitopes have been shown to be more immunogenic than the respective immunogen containing only a single copy of the sequence. It has been unclear, however, whether the increased immunogenicity of a tandemly repeated B-cell epitope necessarily results from increased helper T-cell responses to intrinsic T-cell epitopes in the tandemly repeated sequences, or to neodeterminant T-cell epitopes created at the junction of adjacent repeat sequences. We examined this question by comparing the immunogenicity in mice of two immunogens containing one or eight tandemly repeated copies of an HIV-1 V3 loop haptenic sequence. Our results show that the tandemly repeated haptenic sequence potentiates the immunogenicity of the protein construct, likely through the facilitation of enhanced B-cell interaction with the tandem repeat construct and the consequent elicitation of increased carrier protein-specific helper T-cell responses.
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, 48105, USA. joscher@umich.edu
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D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D015483:HIV Antibodies / Q000096:biosynthesis; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D016882:ISCOMs / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D020449:Repetitive Sequences, Amino Acid; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D002352:Carrier Proteins; D006183:H-2 Antigens; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D006241:Haptens; D016882:ISCOMs; D010455:Peptides