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Distinct effects of recombinant cholera toxin B subunit and holotoxin on different stages of class II MHC antigen processing and presentation by macrophages.
J Immunol. 1996 Jun 01; 156(11):4137-45.JI

Abstract

Cholera toxin (CT) is a potent mucosal adjuvant with enhancing effects on Ag presentation, although the mechanisms of its adjuvanticity remain poorly understood. Using an in vitro Ag presentation assay, we found CT and recombinant B subunit (rCTB) to have distinct effects on different stages of processing and class II MHC (MHC-II)-restricted presentation of hen egg lysozyme (HEL). CT treatment of macrophages resulted in enhanced presentation of soluble HEL(48-61) peptide to3A9 hybridoma cells. However, CT had inhibitory effects on intracellular processing of soluble native Ag. Thus, CT inhibited presentation when added prior to HEL, whereas presentation was enhanced when CT was added after HEL exposure and the generation of peptide-MHC-II complexes. Pretreatment of macrophages with CT also markedly inhibited phagocytic processing of a Crl-HEL fusion protein (containing the HEL(48-61) epitope) expressed in intact bacteria (Escherichia coli HB101.Crl-HEL or Salmonella typhimurium 14028s.Crl-HEL), whereas addition of CT to macrophages after a 2-h incubation with the bacteria again enhanced presentation. CT produced little effect on overall uptake and catabolism of radiolabeled HEL or HB101.Crl-HEL. In contrast to the holotoxin, purified rCTB subunit did not inhibit intracellular processing of soluble or bacterial Ag, although it similarly enhanced the presentation of surface HEL-(48-61)-I-Ak complexes to 3A9 cells. These data suggest that the inhibitory effects of CT on Ag processing are mediated by the A subunit.

Authors+Show Affiliations

Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8666780

Citation

Matousek, M P., et al. "Distinct Effects of Recombinant Cholera Toxin B Subunit and Holotoxin On Different Stages of Class II MHC Antigen Processing and Presentation By Macrophages." Journal of Immunology (Baltimore, Md. : 1950), vol. 156, no. 11, 1996, pp. 4137-45.
Matousek MP, Nedrud JG, Harding CV. Distinct effects of recombinant cholera toxin B subunit and holotoxin on different stages of class II MHC antigen processing and presentation by macrophages. J Immunol. 1996;156(11):4137-45.
Matousek, M. P., Nedrud, J. G., & Harding, C. V. (1996). Distinct effects of recombinant cholera toxin B subunit and holotoxin on different stages of class II MHC antigen processing and presentation by macrophages. Journal of Immunology (Baltimore, Md. : 1950), 156(11), 4137-45.
Matousek MP, Nedrud JG, Harding CV. Distinct Effects of Recombinant Cholera Toxin B Subunit and Holotoxin On Different Stages of Class II MHC Antigen Processing and Presentation By Macrophages. J Immunol. 1996 Jun 1;156(11):4137-45. PubMed PMID: 8666780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct effects of recombinant cholera toxin B subunit and holotoxin on different stages of class II MHC antigen processing and presentation by macrophages. AU - Matousek,M P, AU - Nedrud,J G, AU - Harding,C V, PY - 1996/6/1/pubmed PY - 1996/6/1/medline PY - 1996/6/1/entrez SP - 4137 EP - 45 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 156 IS - 11 N2 - Cholera toxin (CT) is a potent mucosal adjuvant with enhancing effects on Ag presentation, although the mechanisms of its adjuvanticity remain poorly understood. Using an in vitro Ag presentation assay, we found CT and recombinant B subunit (rCTB) to have distinct effects on different stages of processing and class II MHC (MHC-II)-restricted presentation of hen egg lysozyme (HEL). CT treatment of macrophages resulted in enhanced presentation of soluble HEL(48-61) peptide to3A9 hybridoma cells. However, CT had inhibitory effects on intracellular processing of soluble native Ag. Thus, CT inhibited presentation when added prior to HEL, whereas presentation was enhanced when CT was added after HEL exposure and the generation of peptide-MHC-II complexes. Pretreatment of macrophages with CT also markedly inhibited phagocytic processing of a Crl-HEL fusion protein (containing the HEL(48-61) epitope) expressed in intact bacteria (Escherichia coli HB101.Crl-HEL or Salmonella typhimurium 14028s.Crl-HEL), whereas addition of CT to macrophages after a 2-h incubation with the bacteria again enhanced presentation. CT produced little effect on overall uptake and catabolism of radiolabeled HEL or HB101.Crl-HEL. In contrast to the holotoxin, purified rCTB subunit did not inhibit intracellular processing of soluble or bacterial Ag, although it similarly enhanced the presentation of surface HEL-(48-61)-I-Ak complexes to 3A9 cells. These data suggest that the inhibitory effects of CT on Ag processing are mediated by the A subunit. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8666780/Distinct_effects_of_recombinant_cholera_toxin_B_subunit_and_holotoxin_on_different_stages_of_class_II_MHC_antigen_processing_and_presentation_by_macrophages_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=8666780 DB - PRIME DP - Unbound Medicine ER -