HLA-DO: Difference between revisions
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{{infobox protein | |||
| name = [[HLA-DOA|Major Histocompatibility Complex, Class II, DO alpha]] | |||
| caption = | |||
| image = | |||
| width = | |||
| HGNCid = 4936 | |||
| Symbol = [[HLA-DOA]] | |||
| AltSymbols = HLA-DZA, HLA-DNA | |||
| EntrezGene = 3111 | |||
| OMIM = 142930 | |||
| RefSeq = NM_002119 | |||
| UniProt = Q9TQD3 | |||
| PDB = | |||
| ECnumber = | |||
| Chromosome = 6 | |||
| Arm = p | |||
| Band = 21.3 | |||
| LocusSupplementaryData = | |||
}} | |||
{{infobox protein | |||
| Name = [[HLA-DOB|Major Histocompatibility Complex, Class II, DO beta]] | |||
| caption = | |||
| image = | |||
| width = | |||
| HGNCid = 4937 | |||
| Symbol = [[HLA-DOB]] | |||
| AltSymbols = | |||
| EntrezGene = 3112 | |||
| OMIM = 600629 | |||
| RefSeq = NM_002120 | |||
| UniProt = P13765 | |||
| PDB = | |||
| ECnumber = | |||
| Chromosome = 6 | |||
| Arm = p | |||
| Band = 21.3 | |||
| LocusSupplementaryData = | |||
}} | |||
'''Human leukocyte histocompatibility complex DO (HLA-DO)''' is an intracellular, [[Protein dimer|dimeric]] non-classical [[Major Histocompatibility Complex]] (MHC) [[MHC class II|class II]] [[protein]] composed of [[HLA-DOA|α-]] and [[HLA-DOB|β]]-subunits which interact with [[HLA-DM]] in order to fine tune [[Immunodominance|immunodominant]] [[epitope]] selection.<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><ref name=":3" /> As a non-classical MHC class II molecule, HLA-DO is a non-polymorphic accessory protein that aids in [[antigen]]ic peptide [[Chaperone (protein)|chaperoning]] and loading, as opposed to it classical counterparts, which are [[Polymorphism (biology)|polymorphic]] and involved in antigen presentation.<ref name="Poluektov_2013">{{cite journal | vauthors = Poluektov YO, Kim A, Sadegh-Nasseri S | title = HLA-DO and Its Role in MHC Class II Antigen Presentation | journal = Frontiers in Immunology | volume = 4 | pages = 260 | date = September 2013 | pmid = 24009612 | pmc = 3756479 | doi = 10.3389/fimmu.2013.00260 }}</ref><ref name=":1">{{Cite journal|last=Yin|first=Liusong|last2=Stern|first2=Lawrence J.|date=2013-10-17|title=HLA-DM Focuses on Conformational Flexibility Around P1 Pocket to Catalyze Peptide Exchange|journal=Frontiers in Immunology|volume=4|doi=10.3389/fimmu.2013.00336|issn=1664-3224|pmc=3797982|pmid=24146666}}</ref><ref name=":4">{{Cite journal|last=Chen|first=Xinjian|last2=Jensen|first2=Peter E.|date=2014|title=Biological function of HLA-DO (H2-O)|journal=[[Critical Reviews in Immunology]]|volume=34|issue=3|pages=215–225|issn=1040-8401|pmid=24941074}}</ref> Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body—namely, the exclusive expression of HLA-DO in [[B cell]]s, [[Thymus|thymic medullary epithelial cells]], and [[dendritic cell]]s—indicate that it may be of physiological importance and has inspired further research.<ref name="Poluektov_2013" /><ref name=":2">{{Cite journal|last=Denzin|first=Lisa K.|date=2013-12-17|title=Inhibition of HLA-DM Mediated MHC Class II Peptide Loading by HLA-DO Promotes Self Tolerance|journal=Frontiers in Immunology|volume=4|doi=10.3389/fimmu.2013.00465|issn=1664-3224|pmc=3865790|pmid=24381574}}</ref> Moreover, HLA-DO is stable in complex with HLA-DM, and its exhibited instability in the absence of HLA-DM, as well as its evolutionary conservation, further denote its biological significance and potential to confer evolutionary benefits to its host.<ref name=":2" /><ref name="Chen_2003">{{cite journal | vauthors = Chen X, Jensen PE | title = The expression of HLA-DO (H2-O) in B lymphocytes | journal = Immunologic Research | volume = 29 | issue = 1–3 | pages = 19–28 | date = June 2004 | pmid = 15181267 | doi = 10.1385/IR:29:1-3:019 }}</ref><ref name=":0">{{Cite journal|last=Adler|first=Lital N.|last2=Jiang|first2=Wei|last3=Bhamidipati|first3=Kartik|last4=Millican|first4=Matthew|last5=Macaubas|first5=Claudia|last6=Hung|first6=Shu-chen|last7=Mellins|first7=Elizabeth D.|date=2017-03-23|title=The Other Function: Class II-Restricted Antigen Presentation by B Cells|journal=Frontiers in Immunology|volume=8|doi=10.3389/fimmu.2017.00319|issn=1664-3224|pmc=5362600|pmid=28386257}}</ref> | |||
== Discovery == | |||
Studies on HLA-DO [[Transfection|transfected]] [[fibroblast]] cells lines and on the HLA-DO mouse homolog, H-2O, provide most of the current knowledge on the protein.<ref name="Mellins_2913">{{cite journal | vauthors = Mellins ED, Stern LJ | title = HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation | journal = Current Opinion in Immunology | volume = 26 | pages = 115–22 | date = February 2014 | pmid = 24463216 | pmc = 3944065 | doi = 10.1016/j.coi.2013.11.005 }}</ref> In 1985, the [[HLA-DOA|α-]] and [[HLA-DOB|β]]-chains were separately discovered, and in 1990, both chains were found to be co-expressed in one protein in H-2O.<ref name="Chen_2003" /><ref name=":0" /> In contrast to other molecules of MHC class II, [[interferon gamma]] does not induce HLA-DO expression.<ref name="Kuby_2013" /> | |||
== Function == | |||
The binding of HLA-DO at the MHC class II peptide-exchange [[catalysis]] site suggested that it acts as a [[Competitive inhibition|competitive inhibitor]], although biochemical studies have established its complementary function to HLA-DM in fine tuning epitope selection.<ref name="Kuby_2013" /><ref name=":4" /><ref name=":2" /><ref name="Chen_2003" /><ref name="Mellins_2913" /><ref name="Poluektov_2013" /> | |||
During infection, [[Exogenous bacteria|exogenous]] antigen is internalized by [[phagocytosis]] or [[receptor-mediated endocytosis]], and processed in hydrolytic enzyme-containing compartments of increasing acidity.<ref name="Kuby_2013" /><ref name=":0" /> Once the degraded antigen is 13-18 residues, it is ready to bind to MHC class II molecules.<ref name="Kuby_2013" /> To bind to the MHC-class II protein, HLA-DM catalyzes the exchange of [[CLIP protein|CLIP,]] a protein occupying the binding groove of MHC class II, with the antigenic [[oligopeptide]].<ref name="Kuby_2013" /><ref name=":0" /> HLA-DO is strongly associated with HLA-DM throughout the catalyzed exchange.<ref name="Poluektov_2013" /> | |||
== Structure == | |||
Before the three-dimensional structure of complexed HLA-DO was elucidated by [[X-ray crystallography]], its crystal structure was modeled after [[Homology (biology)|homology]] studies to classical MHC class II proteins.<ref name=":1" /><ref name=":0" /><ref name=":3">{{Cite journal|last=Pos|first=Wouter|last2=Sethi|first2=Dhruv K.|last3=Wucherpfennig|first3=Kai W.|date=October 2013|title=Mechanisms of Peptide Repertoire Selection by HLA-DM|journal=Trends in Immunology|volume=34|issue=10|pages=495–501|doi=10.1016/j.it.2013.06.002|issn=1471-4906|pmc=3796002|pmid=23835076}}</ref> Following crystallization of the protein, HLA-DO was found to be conformationally similar to classical MHC class II protein, with alterations in the [[N-terminus]].<ref name=":1" /><ref name="Mellins_2913" /><ref name=":3" /> The structure of the free HLA-DO protein, however, remains to be elucidated.<ref name="Mellins_2913" /> | |||
== References == | |||
{{Reflist|32em}} | |||
{{Surface antigens}} | |||
[[Category:MHC Class II]] | [[Category:MHC Class II]] | ||
Latest revision as of 06:13, 14 June 2018
| Major Histocompatibility Complex, Class II, DO alpha | |
|---|---|
| Identifiers | |
| Symbol | HLA-DOA |
| Alt. symbols | HLA-DZA, HLA-DNA |
| Entrez | 3111 |
| HUGO | 4936 |
| OMIM | 142930 |
| RefSeq | NM_002119 |
| UniProt | Q9TQD3 |
| Other data | |
| Locus | Chr. 6 p21.3 |
| Major Histocompatibility Complex, Class II, DO beta | |
|---|---|
| Identifiers | |
| Symbol | HLA-DOB |
| Entrez | 3112 |
| HUGO | 4937 |
| OMIM | 600629 |
| RefSeq | NM_002120 |
| UniProt | P13765 |
| Other data | |
| Locus | Chr. 6 p21.3 |
Human leukocyte histocompatibility complex DO (HLA-DO) is an intracellular, dimeric non-classical Major Histocompatibility Complex (MHC) class II protein composed of α- and β-subunits which interact with HLA-DM in order to fine tune immunodominant epitope selection.[1][2] As a non-classical MHC class II molecule, HLA-DO is a non-polymorphic accessory protein that aids in antigenic peptide chaperoning and loading, as opposed to it classical counterparts, which are polymorphic and involved in antigen presentation.[3][4][5] Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body—namely, the exclusive expression of HLA-DO in B cells, thymic medullary epithelial cells, and dendritic cells—indicate that it may be of physiological importance and has inspired further research.[3][6] Moreover, HLA-DO is stable in complex with HLA-DM, and its exhibited instability in the absence of HLA-DM, as well as its evolutionary conservation, further denote its biological significance and potential to confer evolutionary benefits to its host.[6][7][8]
Discovery
Studies on HLA-DO transfected fibroblast cells lines and on the HLA-DO mouse homolog, H-2O, provide most of the current knowledge on the protein.[9] In 1985, the α- and β-chains were separately discovered, and in 1990, both chains were found to be co-expressed in one protein in H-2O.[7][8] In contrast to other molecules of MHC class II, interferon gamma does not induce HLA-DO expression.[1]
Function
The binding of HLA-DO at the MHC class II peptide-exchange catalysis site suggested that it acts as a competitive inhibitor, although biochemical studies have established its complementary function to HLA-DM in fine tuning epitope selection.[1][5][6][7][9][3]
During infection, exogenous antigen is internalized by phagocytosis or receptor-mediated endocytosis, and processed in hydrolytic enzyme-containing compartments of increasing acidity.[1][8] Once the degraded antigen is 13-18 residues, it is ready to bind to MHC class II molecules.[1] To bind to the MHC-class II protein, HLA-DM catalyzes the exchange of CLIP, a protein occupying the binding groove of MHC class II, with the antigenic oligopeptide.[1][8] HLA-DO is strongly associated with HLA-DM throughout the catalyzed exchange.[3]
Structure
Before the three-dimensional structure of complexed HLA-DO was elucidated by X-ray crystallography, its crystal structure was modeled after homology studies to classical MHC class II proteins.[4][8][2] Following crystallization of the protein, HLA-DO was found to be conformationally similar to classical MHC class II protein, with alterations in the N-terminus.[4][9][2] The structure of the free HLA-DO protein, however, remains to be elucidated.[9]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 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.
- ↑ 2.0 2.1 2.2 Pos, Wouter; Sethi, Dhruv K.; Wucherpfennig, Kai W. (October 2013). "Mechanisms of Peptide Repertoire Selection by HLA-DM". Trends in Immunology. 34 (10): 495–501. doi:10.1016/j.it.2013.06.002. ISSN 1471-4906. PMC 3796002. PMID 23835076.
- ↑ 3.0 3.1 3.2 3.3 Poluektov YO, Kim A, Sadegh-Nasseri S (September 2013). "HLA-DO and Its Role in MHC Class II Antigen Presentation". Frontiers in Immunology. 4: 260. doi:10.3389/fimmu.2013.00260. PMC 3756479. PMID 24009612.
- ↑ 4.0 4.1 4.2 Yin, Liusong; Stern, Lawrence J. (2013-10-17). "HLA-DM Focuses on Conformational Flexibility Around P1 Pocket to Catalyze Peptide Exchange". Frontiers in Immunology. 4. doi:10.3389/fimmu.2013.00336. ISSN 1664-3224. PMC 3797982. PMID 24146666.
- ↑ 5.0 5.1 Chen, Xinjian; Jensen, Peter E. (2014). "Biological function of HLA-DO (H2-O)". Critical Reviews in Immunology. 34 (3): 215–225. ISSN 1040-8401. PMID 24941074.
- ↑ 6.0 6.1 6.2 Denzin, Lisa K. (2013-12-17). "Inhibition of HLA-DM Mediated MHC Class II Peptide Loading by HLA-DO Promotes Self Tolerance". Frontiers in Immunology. 4. doi:10.3389/fimmu.2013.00465. ISSN 1664-3224. PMC 3865790. PMID 24381574.
- ↑ 7.0 7.1 7.2 Chen X, Jensen PE (June 2004). "The expression of HLA-DO (H2-O) in B lymphocytes". Immunologic Research. 29 (1–3): 19–28. doi:10.1385/IR:29:1-3:019. PMID 15181267.
- ↑ 8.0 8.1 8.2 8.3 8.4 Adler, Lital N.; Jiang, Wei; Bhamidipati, Kartik; Millican, Matthew; Macaubas, Claudia; Hung, Shu-chen; Mellins, Elizabeth D. (2017-03-23). "The Other Function: Class II-Restricted Antigen Presentation by B Cells". Frontiers in Immunology. 8. doi:10.3389/fimmu.2017.00319. ISSN 1664-3224. PMC 5362600. PMID 28386257.
- ↑ 9.0 9.1 9.2 9.3 Mellins ED, Stern LJ (February 2014). "HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation". Current Opinion in Immunology. 26: 115–22. doi:10.1016/j.coi.2013.11.005. PMC 3944065. PMID 24463216.