The Journal of Immunology, Vol 143, Issue 1 29-38, Copyright © 1989 by American Association of Immunologists

ARTICLES

Diminished antigen processing by endosomal acidification mutant antigen- presenting cells

KL McCoy, J Miller, M Jenkins, F Ronchese, RN Germain and RH Schwartz
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.

The role of acidified endosomes in Ag processing was investigated using mutant Chinese hamster ovary cells that express temperature sensitive defects in their acidification mechanism. These cells were transfected with MHC class II genes to convert them to APC. When such mutant cells were incubated at the nonpermissive temperature, losing early endosomal but not lysosomal acidification, their ability to process several native protein Ag was impaired. The nonpermissive temperature did not affect Ag processing by transfected wild type parental cells. Furthermore, T cells were stimulated normally under these conditions when the mutant cells presented antigenic peptide fragments, which do not require processing. The mutant cells were also not defective in the uptake and overall degradation of native antigen. The elimination of Ag processing by paraformaldehyde and chloroquine treatment of the Chinese hamster ovary cells indicates that these cells do not use a different process than physiologic APC. These results suggest that acidification of early endosomes is an important event in Ag processing.

This article has been cited by other articles:

				L. Mortara, P. Castellani, R. Meazza, G. Tosi, A. De Lerma Barbaro, F. A. Procopio, A. Comes, L. Zardi, S. Ferrini, and R. S. Accolla CIITA-Induced MHC Class II Expression in Mammary Adenocarcinoma Leads to a Th1 Polarization of the Tumor Microenvironment, Tumor Rejection, and Specific Antitumor Memory. Clin. Cancer Res., June 1, 2006; 12(11): 3435 - 3443. [Abstract] [Full Text] [PDF]

				R. Thai, G. Moine, M. Desmadril, D. Servent, J.-L. Tarride, A. Menez, and M. Leonetti Antigen Stability Controls Antigen Presentation J. Biol. Chem., November 26, 2004; 279(48): 50257 - 50266. [Abstract] [Full Text] [PDF]

				C. Scheinecker, R. McHugh, E. M. Shevach, and R. N. Germain Constitutive Presentation of a Natural Tissue Autoantigen Exclusively by Dendritic Cells in the Draining Lymph Node J. Exp. Med., October 21, 2002; 196(8): 1079 - 1090. [Abstract] [Full Text] [PDF]

				M. Chen, M. Shirai, Z. Liu, T. Arichi, H. Takahashi, and M. Nishioka Efficient Class II Major Histocompatibility Complex Presentation of Endogenously Synthesized Hepatitis C Virus Core Protein by Epstein-Barr Virus-Transformed B-Lymphoblastoid Cell Lines to CD4+ T Cells J. Virol., October 1, 1998; 72(10): 8301 - 8308. [Abstract] [Full Text] [PDF]

				K. Siemasko, B. J. Eisfelder, E. Williamson, S. Kabak, and M. R. Clark Cutting Edge: Signals from the B Lymphocyte Antigen Receptor Regulate MHC Class II Containing Late Endosomes J. Immunol., June 1, 1998; 160(11): 5203 - 5208. [Abstract] [Full Text] [PDF]

				A. Huang, P Golumbek, M Ahmadzadeh, E Jaffee, D Pardoll, and H Levitsky Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens Science, May 13, 1994; 264(5161): 961 - 965. [Abstract] [PDF]