1YMM

TCR/HLA-DR2b/MBP-peptide complex

Summary for 1YMM

• Entry DOI: 10.2210/pdb1ymm/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DR beta chain, MBP peptide, ... (6 entities in total)
• Functional Keywords: protein-protein complex, t cell repertoire, auto-immunity, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01903; Myelin membrane; Peripheral membrane protein; Cytoplasmic side: P02686; Membrane; Single-pass membrane protein (Potential): P01850
• Total number of polymer chains: 5
• Total formula weight: 98519.68

Authors

Hahn, M.,Nicholson, M.J.,Pyrdol, J.,Wucherpfennig, K.W. (deposition date: 2005-01-21, release date: 2005-05-03, Last modification date: 2024-11-20)

Primary citation

Hahn, M.,Nicholson, M.J.,Pyrdol, J.,Wucherpfennig, K.W.
Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor.
NAT.IMMUNOL., 6:490-496, 2005

PubMed Abstract: Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different from that of antimicrobial TCRs. Rather than being centered on the peptide-major histocompatibility complex, this TCR contacted only the N-terminal peptide segment and made asymmetrical interactions with the major histocompatibility complex helices. The interaction was dominated by the hypervariable complementarity-determining region 3 loops, indicating that unconventional topologies are possible because of the unique complementarity-determining region 3 sequences created during rearrangement. This topology reduces the interaction surface with peptide and alters the geometry for CD4 association. We propose that unusual TCR-binding properties can permit autoreactive T cells to escape deletion.

PubMed: 15821740
DOI: 10.1038/ni1187

Experimental method

X-RAY DIFFRACTION (3.5 Å)