The Journal of Immunology, Vol 145, Issue 3 812-818, Copyright © 1990 by American Association of Immunologists

ARTICLES

MHC class II-restricted presentation of native protein antigen by B cells is inhibitable by cycloheximide and brefeldin A

Y St.-Pierre and TH Watts
Department of Immunology, University of Toronto, Ontario.

The presentation of protein Ag with MHC class II proteins involves the uptake of the protein Ag by endocytosis followed by processing, probably proteolysis, in an intracellular acidic compartment. However, there remains considerable controversy as to the precise route taken by the antigen and the MHC class II protein during this process. The unusual stability of Ag-MHC class II protein complexes has led to speculation that antigen can only associate with newly synthesized MHC class II molecules. An alternate possibility is that the MHC class II binding site can be regenerated within the cell during internalization and recycling of MHC class II proteins. To address these possibilities, three different murine B lymphoma lines were tested for their ability to process and present native protein Ag in the presence of the protein synthesis inhibitor cycloheximide or the protein synthesis inhibitor cycloheximide or the protein export inhibitor, Brefeldin A. Both agents blocked the presentation of native OVA or native hen egg lysozyme to Ag- specific T cell hybridomas. No effect was seen on peptide presentation or on presentation to allo- or autoreactive T cells. Inasmuch as Brefeldin A has been previously shown to block protein export without affecting protein internalization or protein degradation in the endocytic pathway, the simplest interpretation of these data is that antigenic fragments generated in the APC after uptake by the endocytic pathway, preferentially associate with newly synthesized rather than mature MHC class II proteins.

This article has been cited by other articles:

				N. Wang, E. Weber, and J. S. Blum Diminished Intracellular Invariant Chain Expression after Vaccinia Virus Infection J. Immunol., August 1, 2009; 183(3): 1542 - 1550. [Abstract] [Full Text] [PDF]

				J. A. Musson, M. Morton, N. Walker, H. M. Harper, H. V. McNeill, E. D. Williamson, and J. H. Robinson Sequential Proteolytic Processing of the Capsular Caf1 Antigen of Yersinia pestis for Major Histocompatibility Complex Class II-restricted Presentation to T Lymphocytes J. Biol. Chem., September 8, 2006; 281(36): 26129 - 26135. [Abstract] [Full Text] [PDF]

				M. Dugast, H. Toussaint, C. Dousset, and P. Benaroch AP2 Clathrin Adaptor Complex, but Not AP1, Controls the Access of the Major Histocompatibility Complex (MHC) Class II to Endosomes J. Biol. Chem., May 20, 2005; 280(20): 19656 - 19664. [Abstract] [Full Text] [PDF]

				G. Tunheim, K. W. Schjetne, A. B. Fredriksen, I. Sandlie, and B. Bogen Human CD14 is an efficient target for recombinant immunoglobulin vaccine constructs that deliver T cell epitopes J. Leukoc. Biol., March 1, 2005; 77(3): 303 - 310. [Abstract] [Full Text] [PDF]

				L. Ramachandra and C. V. Harding Phagosomes Acquire Nascent and Recycling Class II MHC Molecules but Primarily Use Nascent Molecules in Phagocytic Antigen Processing J. Immunol., May 15, 2000; 164(10): 5103 - 5112. [Abstract] [Full Text] [PDF]

				J. D. Lich, J. F. Elliott, and J. S. Blum Cytoplasmic Processing Is a Prerequisite for Presentation of an Endogenous Antigen by Major Histocompatibility Complex Class II Proteins J. Exp. Med., May 1, 2000; 191(9): 1513 - 1524. [Abstract] [Full Text] [PDF]

				F. Forquet, N. Barois, P. Machy, J. Trucy, V. S. Zimmermann, L. Leserman, and J. Davoust Presentation of Antigens Internalized Through the B Cell Receptor Requires Newly Synthesized MHC Class II Molecules J. Immunol., March 15, 1999; 162(6): 3408 - 3416. [Abstract] [Full Text] [PDF]

				A. A. Delvig and J. H. Robinson Two T Cell Epitopes from the M5 Protein of Viable Streptococcus pyogenes Engage Different Pathways of Bacterial Antigen Processing in Mouse Macrophages J. Immunol., June 1, 1998; 160(11): 5267 - 5272. [Abstract] [Full Text] [PDF]

				N Barois, F Forquet, and J Davoust Actin microfilaments control the MHC class II antigen presentation pathway in B cells J. Cell Sci., January 7, 1998; 111(13): 1791 - 1800. [Abstract] [PDF]

				J. R. Drake, P. Webster, J. C. Cambier, and I. Mellman Delivery of B Cell Receptor-internalized Antigen to Endosomes and Class II Vesicles J. Exp. Med., October 20, 1997; 186(8): 1299 - 1306. [Abstract] [Full Text] [PDF]

				N. Barois, F. Forquet, and J. Davoust Selective Modulation of the Major Histocompatibility Complex Class II Antigen Presentation Pathway following B Cell Receptor Ligation and Protein Kinase C Activation J. Biol. Chem., February 7, 1997; 272(6): 3641 - 3647. [Abstract] [Full Text] [PDF]

				G. Zhong, P. Romagnoli, and R. N. Germain Related Leucine-based Cytoplasmic Targeting Signals in Invariant Chain and Major Histocompatibility Complex Class II Molecules Control Endocytic Presentation of Distinct Determinants in a Single Protein J. Exp. Med., February 3, 1997; 185(3): 429 - 438. [Abstract] [Full Text] [PDF]