PDBsum entry 4x6f

Immune system

PDB id: 4x6f

Contents

Protein chains

263 a.a.

98 a.a.

Ligands

3XU

Waters ×174

PDB id:

4x6f

Name:

Immune system

Title:

Cd1a binary complex with sphingomyelin

Structure:

T-cell surface glycoprotein cd1a. Chain: a. Synonym: t-cell surface antigen t6/leu-6,hta1 thymocyte antigen. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cd1a. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: b2m, cdabp0092, hdcma22p. Expression_system_taxid: 9606

Resolution:

1.91Å R-factor: 0.189 R-free: 0.224

Authors:

R.W.Birkinshaw,J.Rossjohn

Key ref:

R.W.Birkinshaw et al. (2015). αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands. Nat Immunol, 16, 258-266. PubMed id: 25642819 DOI: 10.1038/ni.3098

Date:

08-Dec-14 Release date: 04-Feb-15

Protein chain

P06126  (CD1A_HUMAN) -  T-cell surface glycoprotein CD1a from Homo sapiens

Seq: 327 a.a.

Struc: 263 a.a.*

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 98 a.a.

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1038/ni.3098

Nat Immunol 16:258-266 (2015)

PubMed id: 25642819

αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands.

R.W.Birkinshaw, D.G.Pellicci, T.Y.Cheng, A.N.Keller, M.Sandoval-Romero, S.Gras, A.de Jong, A.P.Uldrich, D.B.Moody, D.I.Godfrey, J.Rossjohn.

ABSTRACT

A central paradigm in αβ T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the αβ T cell antigen receptor (TCR). CD1a presents a broad repertoire of lipid-based antigens. We found that a prototypical autoreactive TCR bound CD1a when it was presenting a series of permissive endogenous ligands, while other lipid ligands were nonpermissive to TCR binding. The structures of two TCR-CD1a-lipid complexes showed that the TCR docked over the A' roof of CD1a in a manner that precluded direct contact with permissive ligands. Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR-CD1a contact zone. The exclusive recognition of CD1a by the TCR represents a previously unknown mechanism whereby αβ T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.