CD74: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}


'''HLA class II histocompatibility antigen gamma chain''' also known as '''HLA-DR antigens-associated invariant chain''' or  '''CD74''' ('''C'''luster of '''D'''ifferentiation 74), is a [[protein]] that in humans is encoded by the ''CD74'' [[gene]].<ref name="pmid6324166">{{cite journal |vauthors=Claesson L, Larhammar D, Rask L, Peterson PA | title = cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 80 | issue = 24 | pages = 7395–9 |date=December 1983 | pmid = 6324166 | pmc = 389957 | doi = 10.1073/pnas.80.24.7395}}</ref><ref name="pmid3001652">{{cite journal |vauthors=Kudo J, Chao LY, Narni F, Saunders GF | title = Structure of the human gene encoding the invariant gamma-chain of class II histocompatibility antigens | journal = Nucleic Acids Res. | volume = 13 | issue = 24 | pages = 8827–41 |date=December 1985 | pmid = 3001652 | pmc = 318954 | doi = 10.1093/nar/13.24.8827}}</ref> The '''invariant chain''' (Abbreviated '''Ii''') is a [[polypeptide]] involved in the formation and transport of [[MHC class II]] protein.<ref name="pmid8011283">{{cite journal | author = Cresswell P | title = Assembly, transport, and function of MHC class II molecules | journal = Annu. Rev. Immunol. | volume = 12 | issue = | pages = 259–93 | year = 1994 | pmid = 8011283 | doi = 10.1146/annurev.iy.12.040194.001355 | url = }}</ref> The cell surface form of the invariant chain is known as CD74.
'''HLA class II histocompatibility antigen gamma chain''' also known as '''HLA-DR antigens-associated invariant chain''' or  '''CD74''' ('''C'''luster of '''D'''ifferentiation 74), is a [[protein]] that in humans is encoded by the ''CD74'' [[gene]].<ref name="pmid6324166">{{cite journal | vauthors = Claesson L, Larhammar D, Rask L, Peterson PA | title = cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 24 | pages = 7395–9 | date = December 1983 | pmid = 6324166 | pmc = 389957 | doi = 10.1073/pnas.80.24.7395 }}</ref><ref name="pmid3001652">{{cite journal | vauthors = Kudo J, Chao LY, Narni F, Saunders GF | title = Structure of the human gene encoding the invariant gamma-chain of class II histocompatibility antigens | journal = Nucleic Acids Research | volume = 13 | issue = 24 | pages = 8827–41 | date = December 1985 | pmid = 3001652 | pmc = 318954 | doi = 10.1093/nar/13.24.8827 }}</ref> The '''invariant chain''' (Abbreviated '''Ii''') is a [[polypeptide]] involved in the formation and transport of [[MHC class II]] protein.<ref name="pmid8011283">{{cite journal | vauthors = Cresswell P | title = Assembly, transport, and function of MHC class II molecules | journal = Annual Review of Immunology | volume = 12 | issue = | pages = 259–93 | year = 1994 | pmid = 8011283 | doi = 10.1146/annurev.iy.12.040194.001355 }}</ref> The cell surface form of the invariant chain is known as CD74.


== Function ==
== Function ==


The nascent [[major histocompatibility complex|MHC]] class II protein in the [[endoplasmic reticulum|rough ER]] binds a segment of the invariant chain (Ii; a trimer) in order to shape the peptide binding groove and prevent formation of a closed conformation. Binding to Ii might also prevent binding of peptides from the endogenous pathway to the groove of MHC class II. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late [[endosome]] containing the endocytosed proteins. It is then cleaved by [[cathepsin S]] ([[cathepsin L]] in cortical thymic epithelial cells), leaving only a small fragment called [[CLIP (protein)|CLIP]] which blocks peptide binding until [[HLA-DM]] interacts with MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface.
The nascent [[major histocompatibility complex|MHC]] class II protein in the [[endoplasmic reticulum|rough ER]] binds a segment of the invariant chain (Ii; a trimer) in order to shape the peptide binding groove and prevent formation of a closed conformation.  
 
The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late [[endosome]] containing the endocytosed antigen proteins (from the exogenous pathway). Binding to Ii ensures that no antigen peptides from the endogenous pathway meant for MHC class I molecules  accidentally bind to the groove of MHC class II molecules.<ref name="Kuby_2013">{{cite book | title = Kuby immunology | vauthors = Owen JA, Punt J, Stranford SA, Jones PP, Kuby J | date = 2013 | publisher = W.H. Freeman | isbn = 978-1-4641-1991-0 | edition = 7th | location = New York | oclc = 820117219}}</ref> The Ii is then cleaved by [[cathepsin S]] ([[cathepsin L]] in cortical thymic epithelial cells), leaving only a small fragment called [[CLIP (protein)|CLIP]] remaining bound to the groove of MHC class II molecules. The rest of the Ii is degraded.<ref name="Kuby_2013" /> CLIP blocks peptide binding until [[HLA-DM]] interacts with MHC II, releasing CLIP and allowing other peptides to bind. In some cases, CLIP dissociates without any further molecular interactions, but in other cases the binding to the MHC is more stable.<ref name="Schulze_2012">{{cite journal | vauthors = Schulze MS, Wucherpfennig KW | title = The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway | journal = Current Opinion in Immunology | volume = 24 | issue = 1 | pages = 105–11 | date = February 2012 | pmid = 22138314 | doi = 10.1016/j.coi.2011.11.004 | pmc = 3288754 }}</ref>
 
The stable MHC class-II with antigen complex is then presented on the cell surface. Without CLIP, MHC class II aggregates, disassemble, and/or denature in the endosomes, and proper antigen presentation is impaired<ref name="Vogt_1999">{{cite journal | vauthors = Vogt AB, Kropshofer H | title = HLA-DM - an endosomal and lysosomal chaperone for the immune system | journal = Trends in Biochemical Sciences | volume = 24 | issue = 4 | pages = 150–4 | date = April 1999 | pmid = 10322421 | doi = 10.1016/s0968-0004(99)01364-x }}</ref>


==Clinical significance==
==Clinical significance==
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===Axial Spondyloarthritis===
===Axial Spondyloarthritis===
[[Autoantibodies]] against CD74 have been identified as a promissing [[biomarkers]] in the early diagnosis of the [[autoimmune disease]] called [[axial spondyloarthritis]] ([[non-radiographic axial Spondyloarthritis]] and [[radiographic axial Spondyloarthritis]] / [[Ankylosing spondylitis]]). <ref>{{cite journal |vauthors=Baerlecken NT, Nothdorft S, Stummvoll GH, Sieper J, Rudwaleit M, Reuter S, Matthias T, Schmidt RE, and Witte T | title = Autoantibodies against CD74 in spondyloarthritis | language = English | journal = Annals of the Rheumatic Diseases | volume = 73 | number = 6 | pages = 1211-14 |date=2014 | doi =10.1136/annrheumdis-2012-202208 }} </ref><ref> {{cite journal |vauthors=Baraliakos X, Baerlecken N, Witte T, Heldmann F, and Braun J | title = High prevalence of anti-CD74 antibodies specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with axial spondyloarthritis | language = English | journal = Annals of the Rheumatic Diseases | volume = 73 | number = 6 | pages = 1079-1082 |date=2014 | doi =10.1136/annrheumdis-2012-202177}}</ref>
[[Autoantibodies]] against CD74 have been identified as a promising [[biomarkers]] in the early diagnosis of the [[autoimmune disease]] called [[axial spondyloarthritis]] ([[non-radiographic axial Spondyloarthritis]] and [[radiographic axial Spondyloarthritis]] / [[Ankylosing spondylitis]]). <ref>{{cite journal | vauthors = Baerlecken NT, Nothdorft S, Stummvoll GH, Sieper J, Rudwaleit M, Reuter S, Matthias T, Schmidt RE, Witte T | title = Autoantibodies against CD74 in spondyloarthritis | language = English | journal = Annals of the Rheumatic Diseases | volume = 73 | issue = 6 | pages = 1211–4 | date = June 2014 | pmid = 23687263 | doi = 10.1136/annrheumdis-2012-202208 }}</ref>


==Possible interactions==
==Interactions==
In limited cases, CD74 might [[Protein-protein interaction|interact]] with [[Macrophage migration inhibitory factor]].<ref>
CD74 receptor [[Protein-protein interaction|interacts]] with the cytokine [[Macrophage migration inhibitory factor]] to mediate its proinflammatory functions<ref>{{cite journal|last1=Moonah|first1=Shannon N.|last2=Abhyankar|first2=Mayuresh M.|last3=Haque|first3=Rashidul|last4=Petri|first4=William A.|last5=Appleton|first5=J. A.|title=The Macrophage Migration Inhibitory Factor Homolog of Entamoeba histolytica Binds to and Immunomodulates Host Macrophages|journal=Infection and Immunity|date=September 2014|volume=82|issue=9|pages=3523–3530|doi=10.1128/IAI.01812-14|pmc=4187827}}</ref>.<ref>
{{cite journal |vauthors=Shan ZX, Lin QX, Deng CY, Tan HH, Kuang SJ, Xiao DZ, Zhu JN, Fu YH, Yu XY | title = [Identification of the interactions between the truncated fragments of macrophage migration inhibitory factor and CD74 using a yeast two-hybrid system] | language = Chinese | journal = Nan Fang Yi Ke Da Xue Xue Bao | volume = 29 | issue = 12 | pages = 2383–6, 2390 |date=December 2009 | pmid = 20034881 | doi = }}
{{cite journal | vauthors = Shan ZX, Lin QX, Deng CY, Tan HH, Kuang SJ, Xiao DZ, Zhu JN, Fu YH, Yu XY | title = [Identification of the interactions between the truncated fragments of macrophage migration inhibitory factor and CD74 using a yeast two-hybrid system] | language = Chinese | journal = Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University | volume = 29 | issue = 12 | pages = 2383–6, 2390 | date = December 2009 | pmid = 20034881 | doi = }}</ref><ref>{{cite journal | vauthors = Wang F, Shen X, Guo X, Peng Y, Liu Y, Xu S, Yang J | title = Spinal macrophage migration inhibitory factor contributes to the pathogenesis of inflammatory hyperalgesia in rats | journal = Pain | volume = 148 | issue = 2 | pages = 275–83 | date = February 2010 | pmid = 20005040 | doi = 10.1016/j.pain.2009.11.011 }}</ref><ref>{{cite journal | vauthors = Dobson SE, Augustijn KD, Brannigan JA, Schnick C, Janse CJ, Dodson EJ, Waters AP, Wilkinson AJ | title = The crystal structures of macrophage migration inhibitory factor from Plasmodium falciparum and Plasmodium berghei | journal = Protein Science | volume = 18 | issue = 12 | pages = 2578–91 | date = December 2009 | pmid = 19827093 | pmc = 2798171 | doi = 10.1002/pro.263 }}</ref><ref>{{cite journal | vauthors = Piette C, Deprez M, Roger T, Noël A, Foidart JM, Munaut C | title = The dexamethasone-induced inhibition of proliferation, migration, and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor (MIF) and can be enhanced by specific MIF inhibitors | journal = The Journal of Biological Chemistry | volume = 284 | issue = 47 | pages = 32483–92 | date = November 2009 | pmid = 19759012 | pmc = 2781663 | doi = 10.1074/jbc.M109.014589 }}</ref><ref>{{cite journal | vauthors = Verjans E, Noetzel E, Bektas N, Schütz AK, Lue H, Lennartz B, Hartmann A, Dahl E, Bernhagen J | title = Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer | journal = BMC Cancer | volume = 9 | pages = 230 | date = July 2009 | pmid = 19602265 | pmc = 2716369 | doi = 10.1186/1471-2407-9-230 }}</ref>
{{cite journal |vauthors=Wang F, Shen X, Guo X, Peng Y, Liu Y, Xu S, Yang J | title = Spinal macrophage migration inhibitory factor contributes to the pathogenesis of inflammatory hyperalgesia in rats | journal = Pain | volume = 148 | issue = 2 | pages = 275–83 |date=February 2010 | pmid = 20005040 | doi = 10.1016/j.pain.2009.11.011 }}
{{cite journal |vauthors=Dobson SE, Augustijn KD, Brannigan JA, Schnick C, Janse CJ, Dodson EJ, Waters AP, Wilkinson AJ | title = The crystal structures of macrophage migration inhibitory factor from Plasmodium falciparum and Plasmodium berghei | journal = Protein Sci. | volume = 18 | issue = 12 | pages = 2578–91 |date=December 2009 | pmid = 19827093 | pmc = 2798171 | doi = 10.1002/pro.263 }}
{{cite journal |vauthors=Piette C, Deprez M, Roger T, Noël A, Foidart JM, Munaut C | title = The Dexamethasone-induced Inhibition of Proliferation, Migration, and Invasion in Glioma Cell Lines Is Antagonized by Macrophage Migration Inhibitory Factor (MIF) and Can Be Enhanced by Specific MIF Inhibitors | journal = J. Biol. Chem. | volume = 284 | issue = 47 | pages = 32483–92 |date=November 2009 | pmid = 19759012 | pmc = 2781663 | doi = 10.1074/jbc.M109.014589 }}
{{cite journal |vauthors=Verjans E, Noetzel E, Bektas N, Schütz AK, Lue H, Lennartz B, Hartmann A, Dahl E, Bernhagen J | title = Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer | journal = BMC Cancer | volume = 9| pages = 230 | year = 2009 | pmid = 19602265 | pmc = 2716369 | doi = 10.1186/1471-2407-9-230 | url = }}</ref>


==See also==
== See also ==
* [[Cluster of differentiation]]
* [[Cluster of differentiation]]
*[[Milatuzumab]] the first Mab to target CD74
*[[Milatuzumab]] the first Mab to target CD74


==References==
== References ==
{{Reflist}}
{{Reflist}}
{{Clear}}
{{Clear}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
*{{cite journal |vauthors=Stove V, Verhasselt B |title=Modelling thymic HIV-1 Nef effects |journal=Curr. HIV Res. |volume=4 |issue= 1 |pages= 57–64 |year= 2006 |pmid= 16454711 |doi=10.2174/157016206775197583 }}
* {{cite journal | vauthors = Stove V, Verhasselt B | title = Modelling thymic HIV-1 Nef effects | journal = Current HIV Research | volume = 4 | issue = 1 | pages = 57–64 | date = January 2006 | pmid = 16454711 | doi = 10.2174/157016206775197583 }}
*{{cite journal | author=Riberdy JM |title=HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides |journal=Nature |volume=360 |issue= 6403 |pages= 474–7 |year= 1992 |pmid= 1448172 |doi= 10.1038/360474a0 |name-list-format=vanc| author2=Newcomb JR  | author3=Surman MJ  | display-authors=3  | last4=Barbosat  | first4=James A.  | last5=Cresswell  | first5=Peter }}
* {{cite journal | vauthors = Riberdy JM, Newcomb JR, Surman MJ, Barbosa JA, Cresswell P | title = HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides | journal = Nature | volume = 360 | issue = 6403 | pages = 474–7 | date = December 1992 | pmid = 1448172 | doi = 10.1038/360474a0 }}
*{{cite journal |vauthors=Bakke O, Dobberstein B |title=MHC class II-associated invariant chain contains a sorting signal for endosomal compartments |journal=Cell |volume=63 |issue= 4 |pages= 707–16 |year= 1990 |pmid= 2121367 |doi=10.1016/0092-8674(90)90137-4  }}
* {{cite journal | vauthors = Bakke O, Dobberstein B | title = MHC class II-associated invariant chain contains a sorting signal for endosomal compartments | journal = Cell | volume = 63 | issue = 4 | pages = 707–16 | date = November 1990 | pmid = 2121367 | doi = 10.1016/0092-8674(90)90137-4 }}
*{{cite journal |vauthors=Marks MS, Blum JS, Cresswell P |title=Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens |journal=J. Cell Biol. |volume=111 |issue= 3 |pages= 839–55 |year= 1990 |pmid= 2391366 |doi=10.1083/jcb.111.3.839  | pmc=2116304 }}
* {{cite journal | vauthors = Marks MS, Blum JS, Cresswell P | title = Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens | journal = The Journal of Cell Biology | volume = 111 | issue = 3 | pages = 839–55 | date = September 1990 | pmid = 2391366 | pmc = 2116304 | doi = 10.1083/jcb.111.3.839 }}
*{{cite journal |vauthors=Spiro RC, Quaranta V |title=The invariant chain is a phosphorylated subunit of class II molecules |journal=J. Immunol. |volume=143 |issue= 8 |pages= 2589–94 |year= 1989 |pmid= 2507633 |doi= }}
* {{cite journal | vauthors = Spiro RC, Quaranta V | title = The invariant chain is a phosphorylated subunit of class II molecules | journal = Journal of Immunology | volume = 143 | issue = 8 | pages = 2589–94 | date = October 1989 | pmid = 2507633 | doi =  }}
*{{cite journal |vauthors=O'Sullivan DM, Noonan D, Quaranta V |title=Four Ia invariant chain forms derive from a single gene by alternate splicing and alternate initiation of transcription/translation |journal=J. Exp. Med. |volume=166 |issue= 2 |pages= 444–60 |year= 1987 |pmid= 3036998 |doi=10.1084/jem.166.2.444  | pmc=2189580  }}
* {{cite journal | vauthors = O'Sullivan DM, Noonan D, Quaranta V | title = Four Ia invariant chain forms derive from a single gene by alternate splicing and alternate initiation of transcription/translation | journal = The Journal of Experimental Medicine | volume = 166 | issue = 2 | pages = 444–60 | date = August 1987 | pmid = 3036998 | pmc = 2189580 | doi = 10.1084/jem.166.2.444 }}
*{{cite journal |vauthors=Genuardi M, Saunders GF |title=Localization of the HLA class II-associated invariant chain gene to human chromosome band 5q32 |journal=Immunogenetics |volume=28 |issue= 1 |pages= 53–6 |year= 1988 |pmid= 3132422 |doi=10.1007/BF00372530  }}
* {{cite journal | vauthors = Genuardi M, Saunders GF | title = Localization of the HLA class II-associated invariant chain gene to human chromosome band 5q32 | journal = Immunogenetics | volume = 28 | issue = 1 | pages = 53–6 | year = 1988 | pmid = 3132422 | doi = 10.1007/BF00372530 }}
*{{cite journal | author=O'Sullivan DM |title=Structure of the human Ia-associated invariant (gamma)-chain gene: identification of 5' sequences shared with major histocompatibility complex class II genes |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 12 |pages= 4484–8 |year= 1986 |pmid= 3459184 |doi=10.1073/pnas.83.12.4484  | pmc=323758  |name-list-format=vanc| author2=Larhammar D  | author3=Wilson MC  | display-authors=3  | last4=Peterson  | first4=PA  | last5=Quaranta  | first5=V  }}
* {{cite journal | vauthors = O'Sullivan DM, Larhammar D, Wilson MC, Peterson PA, Quaranta V | title = Structure of the human Ia-associated invariant (gamma)-chain gene: identification of 5' sequences shared with major histocompatibility complex class II genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 83 | issue = 12 | pages = 4484–8 | date = June 1986 | pmid = 3459184 | pmc = 323758 | doi = 10.1073/pnas.83.12.4484 }}
*{{cite journal |vauthors=Koch N, Hämmerling GJ |title=Ia-associated invariant chain is fatty acylated before addition of sialic acid |journal=Biochemistry |volume=24 |issue= 22 |pages= 6185–90 |year= 1986 |pmid= 3866610 |doi=10.1021/bi00343a023 }}
* {{cite journal | vauthors = Koch N, Hämmerling GJ | title = Ia-associated invariant chain is fatty acylated before addition of sialic acid | journal = Biochemistry | volume = 24 | issue = 22 | pages = 6185–90 | date = October 1985 | pmid = 3866610 | doi = 10.1021/bi00343a023 }}
*{{cite journal |vauthors=Claesson L, Peterson PA |title=Association of human gamma chain with class II transplantation antigens during intracellular transport |journal=Biochemistry |volume=22 |issue= 13 |pages= 3206–13 |year= 1983 |pmid= 6576808 |doi=10.1021/bi00282a026  }}
* {{cite journal | vauthors = Claesson L, Peterson PA | title = Association of human gamma chain with class II transplantation antigens during intracellular transport | journal = Biochemistry | volume = 22 | issue = 13 | pages = 3206–13 | date = June 1983 | pmid = 6576808 | doi = 10.1021/bi00282a026 }}
*{{cite journal |vauthors=Strubin M, Mach B, Long EO |title=The complete sequence of the mRNA for the HLA-DR-associated invariant chain reveals a polypeptide with an unusual transmembrane polarity |journal=EMBO J. |volume=3 |issue= 4 |pages= 869–72 |year= 1984 |pmid= 6586420 |doi=  | pmc=557440  }}
* {{cite journal | vauthors = Strubin M, Mach B, Long EO | title = The complete sequence of the mRNA for the HLA-DR-associated invariant chain reveals a polypeptide with an unusual transmembrane polarity | journal = The EMBO Journal | volume = 3 | issue = 4 | pages = 869–72 | date = April 1984 | pmid = 6586420 | pmc = 557440 | doi =  }}
*{{cite journal | author=Kvist S |title=Membrane insertion and oligomeric assembly of HLA-DR histocompatibility antigens |journal=Cell |volume=29 |issue= 1 |pages= 61–9 |year= 1982 |pmid= 6955026 |doi=10.1016/0092-8674(82)90090-3  |name-list-format=vanc| author2=Wiman K  | author3=Claesson L  | display-authors=3  | last4=Peterson  | first4=Per A.  | last5=Dobberstein  | first5=Bernhard  }}
* {{cite journal | vauthors = Kvist S, Wiman K, Claesson L, Peterson PA, Dobberstein B | title = Membrane insertion and oligomeric assembly of HLA-DR histocompatibility antigens | journal = Cell | volume = 29 | issue = 1 | pages = 61–9 | date = May 1982 | pmid = 6955026 | doi = 10.1016/0092-8674(82)90090-3 }}
*{{cite journal  |vauthors=Machamer CE, Cresswell P |title=Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens |journal=J. Immunol. |volume=129 |issue= 6 |pages= 2564–9 |year= 1983 |pmid= 6982931 |doi=  }}
* {{cite journal | vauthors = Machamer CE, Cresswell P | title = Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens | journal = Journal of Immunology | volume = 129 | issue = 6 | pages = 2564–9 | date = December 1982 | pmid = 6982931 | doi =  }}
*{{cite journal |vauthors=Ghosh P, Amaya M, Mellins E, Wiley DC |title=The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3 |journal=Nature |volume=378 |issue= 6556 |pages= 457–62 |year= 1995 |pmid= 7477400 |doi= 10.1038/378457a0 }}
* {{cite journal | vauthors = Ghosh P, Amaya M, Mellins E, Wiley DC | title = The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3 | journal = Nature | volume = 378 | issue = 6556 | pages = 457–62 | date = November 1995 | pmid = 7477400 | doi = 10.1038/378457a0 }}
*{{cite journal |vauthors=Bijlmakers MJ, Benaroch P, Ploegh HL |title=Mapping functional regions in the lumenal domain of the class II- associated invariant chain |journal=J. Exp. Med. |volume=180 |issue= 2 |pages= 623–9 |year= 1994 |pmid= 7519244 |doi=10.1084/jem.180.2.623  | pmc=2191624  }}
* {{cite journal | vauthors = Bijlmakers MJ, Benaroch P, Ploegh HL | title = Mapping functional regions in the lumenal domain of the class II-associated invariant chain | journal = The Journal of Experimental Medicine | volume = 180 | issue = 2 | pages = 623–9 | date = August 1994 | pmid = 7519244 | pmc = 2191624 | doi = 10.1084/jem.180.2.623 }}
*{{cite journal | author=Brown JH |title=Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1 |journal=Nature |volume=364 |issue= 6432 |pages= 33–9 |year= 1993 |pmid= 8316295 |doi= 10.1038/364033a0  |name-list-format=vanc| author2=Jardetzky TS  | author3=Gorga JC  | display-authors=3  | last4=Stern  | first4=Lawrence J. | last5=Urban  | first5=Robert G.  | last6=Strominger  | first6=Jack L.  | last7=Wiley  | first7=Don C. }}
* {{cite journal | vauthors = Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC | title = Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1 | journal = Nature | volume = 364 | issue = 6432 | pages = 33–9 | date = July 1993 | pmid = 8316295 | doi = 10.1038/364033a0 }}
*{{cite journal  | author=Naujokas MF |title=The chondroitin sulfate form of invariant chain can enhance stimulation of T cell responses through interaction with CD44 |journal=Cell |volume=74 |issue= 2 |pages= 257–68 |year= 1993 |pmid= 8343954 |doi=10.1016/0092-8674(93)90417-O  |name-list-format=vanc| author2=Morin M  | author3=Anderson MS  | display-authors=3  | last4=Peterson  | first4=Mary  | last5=Miller  | first5=Jim  }}
* {{cite journal | vauthors = Naujokas MF, Morin M, Anderson MS, Peterson M, Miller J | title = The chondroitin sulfate form of invariant chain can enhance stimulation of T cell responses through interaction with CD44 | journal = Cell | volume = 74 | issue = 2 | pages = 257–68 | date = July 1993 | pmid = 8343954 | doi = 10.1016/0092-8674(93)90417-O }}
*{{cite journal  | author=Roche PA |title=Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 18 |pages= 8581–5 |year= 1993 |pmid= 8397411 |doi=10.1073/pnas.90.18.8581  | pmc=47401  |name-list-format=vanc| author2=Teletski CL  | author3=Stang E  | display-authors=3  | last4=Bakke  | first4=O  | last5=Long  | first5=EO  }}
* {{cite journal | vauthors = Roche PA, Teletski CL, Stang E, Bakke O, Long EO | title = Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 18 | pages = 8581–5 | date = September 1993 | pmid = 8397411 | pmc = 47401 | doi = 10.1073/pnas.90.18.8581 }}
{{refend}}
{{refend}}


==External links==
== External links ==
* {{MeshName|CD74+protein,+human}}
* {{MeshName|CD74+protein,+human}}
* [http://www.bio.davidson.edu/Courses/immunology/Students/spring2006/McCracken/HLA-DM.html Overview] at [[Davidson College]] (student generated)
* [http://www.bio.davidson.edu/Courses/immunology/Students/spring2006/McCracken/HLA-DM.html Overview] at [[Davidson College]] (student generated)

Latest revision as of 11:23, 11 October 2018

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HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74 (Cluster of Differentiation 74), is a protein that in humans is encoded by the CD74 gene.[1][2] The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II protein.[3] The cell surface form of the invariant chain is known as CD74.

Function

The nascent MHC class II protein in the rough ER binds a segment of the invariant chain (Ii; a trimer) in order to shape the peptide binding groove and prevent formation of a closed conformation.

The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed antigen proteins (from the exogenous pathway). Binding to Ii ensures that no antigen peptides from the endogenous pathway meant for MHC class I molecules accidentally bind to the groove of MHC class II molecules.[4] The Ii is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP remaining bound to the groove of MHC class II molecules. The rest of the Ii is degraded.[4] CLIP blocks peptide binding until HLA-DM interacts with MHC II, releasing CLIP and allowing other peptides to bind. In some cases, CLIP dissociates without any further molecular interactions, but in other cases the binding to the MHC is more stable.[5]

The stable MHC class-II with antigen complex is then presented on the cell surface. Without CLIP, MHC class II aggregates, disassemble, and/or denature in the endosomes, and proper antigen presentation is impaired[6]

Clinical significance

Cancer

Found on a number of cancer cell types. Possible cancer therapy target. See Milatuzumab#CD74

Axial Spondyloarthritis

Autoantibodies against CD74 have been identified as a promising biomarkers in the early diagnosis of the autoimmune disease called axial spondyloarthritis (non-radiographic axial Spondyloarthritis and radiographic axial Spondyloarthritis / Ankylosing spondylitis). [7]

Interactions

CD74 receptor interacts with the cytokine Macrophage migration inhibitory factor to mediate its proinflammatory functions[8].[9][10][11][12][13]

See also

References

  1. ↑ Claesson L, Larhammar D, Rask L, Peterson PA (December 1983). "cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure". Proceedings of the National Academy of Sciences of the United States of America. 80 (24): 7395–9. doi:10.1073/pnas.80.24.7395. PMC 389957. PMID 6324166.
  2. ↑ Kudo J, Chao LY, Narni F, Saunders GF (December 1985). "Structure of the human gene encoding the invariant gamma-chain of class II histocompatibility antigens". Nucleic Acids Research. 13 (24): 8827–41. doi:10.1093/nar/13.24.8827. PMC 318954. PMID 3001652.
  3. ↑ Cresswell P (1994). "Assembly, transport, and function of MHC class II molecules". Annual Review of Immunology. 12: 259–93. doi:10.1146/annurev.iy.12.040194.001355. PMID 8011283.
  4. ↑ 4.0 4.1 Owen JA, Punt J, Stranford SA, Jones PP, Kuby J (2013). Kuby immunology (7th ed.). New York: W.H. Freeman. ISBN 978-1-4641-1991-0. OCLC 820117219.
  5. ↑ Schulze MS, Wucherpfennig KW (February 2012). "The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway". Current Opinion in Immunology. 24 (1): 105–11. doi:10.1016/j.coi.2011.11.004. PMC 3288754. PMID 22138314.
  6. ↑ Vogt AB, Kropshofer H (April 1999). "HLA-DM - an endosomal and lysosomal chaperone for the immune system". Trends in Biochemical Sciences. 24 (4): 150–4. doi:10.1016/s0968-0004(99)01364-x. PMID 10322421.
  7. ↑ Baerlecken NT, Nothdorft S, Stummvoll GH, Sieper J, Rudwaleit M, Reuter S, Matthias T, Schmidt RE, Witte T (June 2014). "Autoantibodies against CD74 in spondyloarthritis". Annals of the Rheumatic Diseases. 73 (6): 1211–4. doi:10.1136/annrheumdis-2012-202208. PMID 23687263.
  8. ↑ Moonah, Shannon N.; Abhyankar, Mayuresh M.; Haque, Rashidul; Petri, William A.; Appleton, J. A. (September 2014). "The Macrophage Migration Inhibitory Factor Homolog of Entamoeba histolytica Binds to and Immunomodulates Host Macrophages". Infection and Immunity. 82 (9): 3523–3530. doi:10.1128/IAI.01812-14. PMC 4187827.
  9. ↑ Shan ZX, Lin QX, Deng CY, Tan HH, Kuang SJ, Xiao DZ, Zhu JN, Fu YH, Yu XY (December 2009). "[Identification of the interactions between the truncated fragments of macrophage migration inhibitory factor and CD74 using a yeast two-hybrid system]". Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University (in Chinese). 29 (12): 2383–6, 2390. PMID 20034881.
  10. ↑ Wang F, Shen X, Guo X, Peng Y, Liu Y, Xu S, Yang J (February 2010). "Spinal macrophage migration inhibitory factor contributes to the pathogenesis of inflammatory hyperalgesia in rats". Pain. 148 (2): 275–83. doi:10.1016/j.pain.2009.11.011. PMID 20005040.
  11. ↑ Dobson SE, Augustijn KD, Brannigan JA, Schnick C, Janse CJ, Dodson EJ, Waters AP, Wilkinson AJ (December 2009). "The crystal structures of macrophage migration inhibitory factor from Plasmodium falciparum and Plasmodium berghei". Protein Science. 18 (12): 2578–91. doi:10.1002/pro.263. PMC 2798171. PMID 19827093.
  12. ↑ Piette C, Deprez M, Roger T, Noël A, Foidart JM, Munaut C (November 2009). "The dexamethasone-induced inhibition of proliferation, migration, and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor (MIF) and can be enhanced by specific MIF inhibitors". The Journal of Biological Chemistry. 284 (47): 32483–92. doi:10.1074/jbc.M109.014589. PMC 2781663. PMID 19759012.
  13. ↑ Verjans E, Noetzel E, Bektas N, Schütz AK, Lue H, Lennartz B, Hartmann A, Dahl E, Bernhagen J (July 2009). "Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer". BMC Cancer. 9: 230. doi:10.1186/1471-2407-9-230. PMC 2716369. PMID 19602265.

Further reading

External links

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