Document Detail


Processing of an antigenic sequence from IgG constant domains for presentation by MHC class II.
MedLine Citation:
PMID:  18981126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Targeting of T cell epitopes to APC enhances T cell responses. We used an APC-specific Ab (anti-IgD) and substituted either of 18 loops connecting beta strands in human IgG constant H (C(H)) domains with a characterized T cell peptide epitope. All Ab-epitope fusion molecules were secreted from producing cells except IgG-loop 2(BC)C(H)1, and comparing levels, a hierarchy appeared with fusions involving C(H)2 > or = C(H)1 > C(H)3. Within each domain, fusion at loop 6(FG) showed best secretion, while low secretion correlated with the substitution of native loops that contain conserved amino acids buried within the folded molecule. Comparing the APC-specific rAb molecules for their ability to induce T cell activation in vitro, the six mutants with epitope in C(H)2 were the most effective, with loop 4C(H)2 ranking on top. The C(H)1 mutants were more resistant to processing, and the loop 6C(H)1 mutant only induced detectable activation. The efficiency of the C(H)3 mutants varied, with loop 6C(H)3 being the least effective and equal to loop 6 C(H)1. Considering both rAb secretion level and T cell activation efficiency, a total of eight loops may carry T cell epitopes to APC for processing and presentation to T cells, namely, all in C(H)2 in addition to loop 6 in C(H)1 and C(H)3. Comparing loop 4C(H)2 with loop 6C(H)1 mutants after injection of Ab in BALB/c mice, the former was by far the most efficient and induced specific T cell activation at concentrations at least 100-fold lower than loop 6C(H)1.
Authors:
Morten Flobakk; Ingunn B Rasmussen; Elin Lunde; Terje Frigstad; Gøril Berntzen; Terje E Michaelsen; Bjarne Bogen; Inger Sandlie
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  181     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-04     Completed Date:  2008-12-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7062-72     Citation Subset:  AIM; IM    
Affiliation:
Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen Presentation / immunology*
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Epitopes, T-Lymphocyte / immunology*
Histocompatibility Antigens Class II / immunology*
Humans
Immunoglobulin Constant Regions / chemistry,  immunology*
Immunoglobulin G / chemistry,  immunology*
Lymphocyte Activation / immunology*
Mice
Mice, Inbred BALB C
Protein Structure, Secondary
Recombinant Fusion Proteins / chemical synthesis,  chemistry,  immunology
Chemical
Reg. No./Substance:
0/Epitopes, T-Lymphocyte; 0/Histocompatibility Antigens Class II; 0/Immunoglobulin Constant Regions; 0/Immunoglobulin G; 0/Recombinant Fusion Proteins

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