Journal article
Conformational alterations during biosynthesis of HLA-DR3 molecules controlled by invariant chain and HLA-DM
European journal of immunology, v 31(4), pp 1029-1036
Apr 2001
PMID: 11298327
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
HLA-DM is known to catalyze the exchange of class II-associated invariant chain (Ii) peptide (CLIP) for cognate peptide during biosynthesis. In DM-negative cells HLA-DR3 molecules have been shown to predominantly present CLIP and to lack the DR3-specific mAb epitope 16.23, which has led to the assumption that CLIP prevents binding of mAb 16.23. In the present study we show that CLIP does not prohibit 16.23 epitope expression, but that the formation of this epitope is directly influenced by interactions of the DR molecule with Ii and DM. Detergent solubilized DR3 from wild-type as well as DM(-) cells bound CLIP in a 16.23(+) mode. On cells, however, neither CLIP nor antigenic peptide bound to DR3 in a 16.23(+) conformation, unless HLA-DM was expressed. Thus, HLA-DM appears to alter the conformation of DR3 in a peptide-independent fashion. Since in DM-deficient cells that also lack Ii, DR3 molecules assembled in a 16.23(+) conformation, we conclude that during biosynthesis Ii and DM exert opposing conformational constraints, characterized by suppressing or releasing 16.23 epitope expression. These results imply that DR3/peptide complexes, including DR3/ CLIP, can exist in two conformations depending on previous interaction with DM, but independent of the nature of the peptide bound. We show that these naturally occurring class II conformers can be selectively recognized by T cells.
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Details
- Title
- Conformational alterations during biosynthesis of HLA-DR3 molecules controlled by invariant chain and HLA-DM
- Creators
- F A Verreck - HeidelbergC A FargeasG J HämmerlingIrwin M Chaiken - Biochemistry and Molecular Biology
- Publication Details
- European journal of immunology, v 31(4), pp 1029-1036
- Publisher
- Wiley
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Drexel University
- Web of Science ID
- WOS:000168090100007
- Other Identifier
- 991019520423604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology