Perraudeau, M., Taylor, P. R., Stauss, H. J., Lindstedt, R., Bygrave, A. E., Pappin, D. J., Ellmerich, S., Whitten, A., Rahman, D., Canas, B., Walport, M. J., Botto, M., Altmann, D. M. (October 2000) Altered major histocompatibility complex class II peptide loading in H2-O-deficient mice. Eur J Immunol, 30 (10). pp. 2871-80. ISSN 0014-2980 (Print)0014-2980 (Linking)
Abstract
The biosynthesis of MHC class II/peptide complexes involves classical, cell surface MHC products as well as the intracellular component H2-M, required for the removal of invariant chain-derived CLIP and for peptide loading. The function of another intracellular class II heterodimer, H2-O, is the matter of some controversy. The physical association of H2-O with H2-M and co-localization in class II+ vesicles suggest a related function in peptide exchange. Furthermore, the distinctive thymic distribution of H2-O raises the possibility of a specialized role in T cell thymic selection. To investigate the role of H2-O in vivo we generated mice carrying a targeted disruption in the H2-Oa gene. No evidence was obtained for a defect in removal of CLIP. However, the array of endogenous peptides bound by class II was altered and a defect in antigen presentation through H2-A to T cells was seen on the 129/Sv/ C57BL/6 mixed strain background but not in 129/Sv pure strain mice. Furthermore, H2-O-null mice showed enhanced selection of CD4+ single positive thymocytes. The findings indicate that H2-O interacts with H2-M in peptide editing but that the genetic background in which H2-O deficiency is manifest is also important. Overall, the experiments indicate that H2-O/HLA-DO should be regarded as neither up-regulating nor down-regulating the DM-dependent release of CLIP, but as a modulator of peptide editing, determining the presenting cell type specific peptide profile able to retain stability in the class II groove.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Antigen Presentation Antigens/immunology/metabolism Antigens, CD4/immunology Antigens, CD8/immunology Antigens, Differentiation, B-Lymphocyte/metabolism Dimerization Female Genes, MHC Class II Genotype Histocompatibility Antigens Class II/genetics/ immunology/metabolism Mice Mice, Inbred C57BL Mice, Knockout Peptide Fragments/immunology/ metabolism Protein Binding Receptors, Antigen, T-Cell, alpha-beta/genetics Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization T-Lymphocyte Subsets/immunology |
| Subjects: | organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal |
| CSHL Authors: | |
| Communities: | CSHL labs > Pappin lab |
| Depositing User: | Matt Covey |
| Date: | October 2000 |
| Date Deposited: | 31 Jan 2014 20:32 |
| Last Modified: | 31 Jan 2014 20:32 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/29348 |
Actions (login required)
 |
Administrator's edit/view item |