CD74

from Wikipedia, the free encyclopedia
HLA class II histocompatibility antigen gamma chain
HLA class II histocompatibility antigen gamma chain
according to PDB  1ICF
other names

HLA-DR antigens-associated invariant chain, Ia antigen-associated invariant chain, Ii

Existing structural data : PDB  1A6A , PDB  1IIE

Properties of human protein
Mass / length primary structure 296 amino acids , 33,516 Da
Identifier
External IDs
Orthologue (human)
Entrez 972
Ensemble ENSG00000019582
UniProt P04233
Refseq (mRNA) NM_001025158.2
Refseq (protein) NP_001020329.1
Gene locus Chr 5: 150.4 - 150.41 Mb
PubMed search 972

CD74 (synonymous HLA class II histocompatibility antigen γ chain ) is a surface protein from the group of the main histocompatibility complexes of class II in humans ( MHCII in other vertebrates ). It is involved in the antigen presentation in the course of an immune response .

properties

CD74 binds in the endoplasmic reticulum to heterodimers made up of α- and β-chains of HLAII and stabilizes them if no antigen is bound. CD74 is a chaperone for MHCII proteins and stabilizes their protein folding . The bound heterodimers are then pinched off from the endoplasmic reticulum to form an endosome . The signal for transport is in the cytosolic region of CD74. The endosome is then fused with an endolysosome . In endolysosom CD74 is determined by the proteases cathepsin S or cortical cells in the thymus by Cathepsin L split. A short fragment of the CD74 ( CLIP ) blocks the binding of antigens to MHCII until binding by HLA-DM to MHCII occurs, which releases the CLIP again. The complex is then presented to the immune cells on the cell membrane . In contrast to some other MHCII, CD74 has no polymorphisms . CD74 is glycosylated and phosphorylated .

CD74 is also the receptor for MIF , D-dopachrome tautomerase (synonym MIF-2 ) and bacterial proteins. In contrast to the name MIF-2, this binding partner of CD74 promotes inflammation. The protein Vpu of HIV binds to CD74. It is involved in the transport of the angiotensin II type I receptor to the cell membrane. Furthermore, CD74 is involved in the regulation of the development of T cells and B cells , in the motility of dendritic cells , the activation of macrophages and the negative selection of T cells in the thymus . CD74 is produced in T cells and macrophages, but also in non-immune cells such as endothelial cells and epithelial cells of the kidneys of the intestine and skin .

CD74 is produced to an increased extent by some tumors and is associated with increased metastasis . In the autoimmune disease axial spondyloarthritis , autoantibodies against CD74 are formed, which are also used for diagnosis.

The antibody milatuzumab binds to CD74 and is being studied as an immunoconjugate with doxorubicin for the treatment of multiple myeloma .

Web links

Individual evidence

  1. ↑ a b c d H. Su, N. Na, X. Zhang, Y. Zhao: The biological function and significance of CD74 in immune diseases. In: Inflammation research: official journal of the European Histamine Research Society .. [et al.]. Volume 66, Number 3, March 2017, pp. 209-216, doi : 10.1007 / s00011-016-0995-1 , PMID 27752708 .
  2. ↑ a b B. Schröder: The multifaceted roles of the invariant chain CD74 - More than just a chaperone. In: Biochimica et Biophysica Acta . Volume 1863, number 6 Pt A, June 2016, pp. 1269–1281, doi : 10.1016 / j.bbamcr.2016.03.026 , PMID 27033518 .
  3. ↑ a b G. Grieb, BS Kim, D. Simons, J. Bernhagen, N. Pallua: MIF and CD74 - suitability as clinical biomarkers. In: Mini reviews in medicinal chemistry. Volume 14, Number 14, 2014, pp. 1125-1131, PMID 25643609 .
  4. ↑ DA Le Noury, S. Mosebi, MA Papathanasopoulos, R. Hewer: Functional roles of HIV-1 Vpu and CD74: Details and implications of the Vpu-CD74 interaction. In: Cellular immunology. Volume 298, number 1–2, 2015 Nov-Dec, pp. 25–32, doi : 10.1016 / j.cellimm.2015.08.005 , PMID 26321123 .
  5. ↑ Baerlecken NT, Nothdorft S, Stummvoll GH, Sieper J, Rudwaleit M, Reuter S, Matthias T, Schmidt RE, and Witte T: Autoantibodies against CD74 in spondyloarthritis . In: Annals of the Rheumatic Diseases . 73 (6), 2014, pp. 1211-14. doi : 10.1136 / annrheumdis-2012-202208 .
  6. ↑ Baraliakos X, Baerlecken N, Witte T, Heldmann F, and Braun J: High prevalence of anti-CD74 antibodies specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with axial spondyloarthritis . In: Annals of the Rheumatic Diseases . 73 (6), 2014, pp. 1079-1082. doi : 10.1136 / annrheumdis-2012-202177 .
  7. ↑ P. Robak, T. Robak: Management of Multiple Myeloma with Second-Generation Antibody-Drug Conjugates. In: BioDrugs: clinical immunotherapeutics, biopharmaceuticals and gene therapy. Volume 30, Number 2, April 2016, pp. 87-93, doi : 10.1007 / s40259-016-0165-6 , PMID 26927803 .