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<StructureSection load='' size='350' side='right' caption='Human MHC class I antigen (cyan) with β 2-microglobulin (green) and peptide from Hepatitis virus (deeppink) [[3ox8]]' scene='45/457390/Cv/1'>
<StructureSection load='' size='350' side='right' caption='Human MHC class I antigen (cyan) with β 2-microglobulin (green) and peptide from Hepatitis virus (deeppink) [[3ox8]]' scene='45/457390/Cv/7'>
__TOC__
== Function ==
== Function ==
''' Major Histocompatibility Complex''' (MHC) are part of the cell immune system.  MHC molecules display antigens on the host cell’s surface. T cell or natural killer receptors recognize the MHC:peptide and activate the immune response.<br />
''' Major Histocompatibility Complex''' (MHC) molecules bind peptides derived from degraded proteins and present these peptides on the surface of the cell. Cytotoxic T-lymphocytes or helper T cells recognize the MHC:peptide complex on the surface of the cell and, if the presented peptide (antigen) is suggestive of a pathogenic or foreign protein, trigger an immune response. In this way, MHC molecules allow for immune system detection of cellular activity, making them an essential part of the organism’s immune system. MHC molecules are divided into Class I and Class II molecules based on the types of cells that typically express them and the types of peptides they typically bind. 
*  '''MHC class I''' ([[Major Histocompatibility Complex Class I]]) are found in all nucleated cells.  These cell surface proteins display peptides from cellular intrinsic proteins<ref>PMID:18675588</ref>.  For more details see <br />
<br />
*[[Effect of HCMV on Major Histocompatibility Complex Class I]]<br />
*  '''MHC class I''' ([[Major Histocompatibility Complex Class I]]) are found in all nucleated cells and platelets.  These cell surface proteins display peptides from cellular intrinsic proteins<ref>PMID:18675588</ref><ref> DOI: 10.1074/jbc.RA119.010251 </ref>.  For more details see <br />
*[[MR1 Binds Vitamin Metabolites]].<br />
**[[Effect of HCMV on Major Histocompatibility Complex Class I]]<br />
**[[MR1 Binds Vitamin Metabolites]].<br />
*  '''MHC class II''' are found in professional antigen-presenting cells like macrophages.  These cell surface proteins display peptides from cellular extrinsic proteins<ref>PMID:15120183</ref>.<br />
*  '''MHC class II''' are found in professional antigen-presenting cells like macrophages.  These cell surface proteins display peptides from cellular extrinsic proteins<ref>PMID:15120183</ref>.<br />
For MHC class II interactions with T-cell receptor and gliadin peptide see [[SP3.4-TCR-HLA-DQ8-α-1-gliadin complex]].
For information on MHC class II interactions with T-cell receptor and gliadin peptide see [[SP3.4-TCR-HLA-DQ8-α-1-gliadin complex]].


== Structural highlights ==
== Structural highlights ==
 
Both Class I and Class II MHC molecules are heterodimers with two extracellular subunits (α and β) and one or two transmembrane helices that extend from the extracellular subunits to the cytoplasm. In Class I molecules, the α subunit is divided into three domains (α<sub>1</sub>, α<sub>2</sub>, and α<sub>3</sub>). The α<sub>1</sub> and α<sub>2</sub> domains together form an eight strand β-sheet platform and two α-helix rails that serve as the peptide-binding groove. The α<sub>3</sub> domain forms an immunoglobulin-like fold that carries the peptide-binding groove with added support from with the β subunit (a β<sub>2</sub>-microglobulin molecule encoded outside of the MHC Class I gene locus). In Class II molecules, both the α and β subunits are divided into two domains (α<sub>1</sub>, α<sub>2</sub>,β<sub>1</sub>, and β<sub>2</sub>). The peptide-binding groove is formed by the α<sub>1</sub> and β<sub>1</sub> domains. The α<sub>2</sub> and β<sub>2</sub> domains carry the peptide-binding groove. Unlike the β subunits of Class I molecules, the β subunits of Class II molecules are encoded within the MHC Class II gene. While the α subunit is polymorphic for both MHC Classes, the β subunit is polymorphic only for Class II molecules.
<scene name='45/457390/Cv/5'>Human MHC class I antigen with β 2-microglobulin and peptide from Hepatitis virus</scene>.  
<scene name='45/457390/Cv/5'>Human MHC class I antigen with β 2-microglobulin and peptide from Hepatitis virus</scene>.  
The <scene name='45/457390/Cv/6'>peptide derived from Hepatitis virus binds MHC in a peptide-recognition groove and makes various interactions with side chains and with water molecules</scene><ref>PMID:21538979</ref>. Water molecules shown as red spheres.  
The <scene name='45/457390/Cv/6'>peptide derived from Hepatitis virus binds MHC in a peptide-recognition groove and makes various interactions with side chains and with water molecules</scene><ref>PMID:21538979</ref>. Water molecules shown as red spheres.  
</StructureSection>


==3D structures of MHC==
==List of Published 3D Structures of MHC==
[[MHC I 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
[[MHC II 3D structures]]
{{#tree:id=OrganizedByTopic|openlevels=0|
</StructureSection>
 
*'''MHC I'''
 
*MHC I binary complex
 
**[[1zs8]] - mMHC  I + β-2-microglobulin – mouse<br />
**[[2hla]], [[3hla]], [[1hla]] - hMHC  I + β-2-microglobulin – human<br />
**[[3p73]], [[3p77]] - cMHC  I + β-2-microglobulin – chicken
 
*MHC I ternary complex
 
**[[4d0b]], [[3bew]], [[2yez]], [[5ad0]], [[4d0c]], [[3bev]], [[4cvx]] – cMHC I α + β-2-microglobulin + peptide<br />
**[[3kpn]], [[3kpo]] – hMHC I B + β-2-microglobulin + peptide<br />
**[[3bev]], [[1kpr]], [[1k5n]], [[3nfn]], [[3mr9]], [[3mrb]], [[3mrc]], [[3mrd]], [[3mre]], [[3mrf]], [[3mrg]], [[3mrh]], [[3mri]], [[3mrj]], [[3mrk]], [[3mrl]], [[3mrm]], [[3mrn]], [[3mro]], [[3mrp]], [[3mrq]], [[3mrr]], [[3ox8]], [[3oxr]], [[3oxs]], [[2xpg]], [[3pwj]], [[3pwl]], [[3pwn]], [[3pwp]], [[2x70]], [[3o3a]], [[3o3b]], [[3o3d]], [[3o3e]], [[3lv3]], [[3ln4]], [[3ln5]], [[3myj]], [[3i6l]], [[3lkn]], [[3lko]], [[3lkp]], [[3lkq]], [[3lkr]], [[3lks]], [[3hpj]], [[3i6g]], [[3i6k]], [[3mgo]], [[3mgt]], [[3l3d]], [[3l3g]], [[3l3i]], [[3l3j]], [[3l3k]], [[2x4n]], [[2x4o]], [[2x4p]], [[2x4q]], [[2x4r]], [[2x4s]], [[2x4t]], [[2x4u]], [[3lka]], [[3h7b]], [[3kpl]], [[3kpm]], [[3kpn]], [[3kpo]], [[3kpp]], [[3kpq]], [[3kpr]], [[3kps]], [[3giv]], [[3hcv]], [[3d18]], [[3dtx]], [[3czf]], [[3fqn]], [[3fqr]], [[3fqt]], [[3fqu]], [[3fqw]], [[3fqx]], [[3d25]], [[3bvn]], [[3dx6]], [[3dx7]], [[3dx8]], [[3dxa]], [[3bo8]], [[3bp4]], [[3bp7]], [[3bgm]], [[3bh8]], [[3bh9]], [[3bhb]], [[3b3i]], [[3b6s]], [[2rfx]], [[3bze]], [[3bzf]], [[3bw9]], [[3bwa]], [[3c9n]], [[2v2w]], [[2v2x]], [[2gt9]], [[2gtw]], [[2gtz]], [[2guo]], [[2nw3]], [[2fyy]], [[2fz3]], [[2hn7]], [[2cik]], [[2git]], [[2hjk]], [[2hjl]], [[2h6p]], [[2d31]], [[2c7u]], [[2bck]], [[2a83]], [[2axf]], [[2axg]], [[2bvo]], [[2bvp]], [[2bvq]], [[1s8d]], [[1t1w]], [[1t1x]], [[1t1y]], [[1t1z]], [[1t20]], [[1t21]], [[1t22]], [[1s7q]], [[1zsd]], [[2bsr]], [[2bss]], [[2bst]], [[1zhk]], [[1zhl]], [[1tvb]], [[1tvh]], [[1xr8]], [[1xr9]], [[1w0v]], [[1w0w]], [[1xh3]], [[1uxs]], [[1uxw]], [[1s9w]], [[1s9x]], [[1s9y]], [[1q94]], [[1qvo]], [[1n2r]], [[1ogt]], [[1qew]], [[1jge]], [[1k5n]], [[1i7r]], [[1i7t]], [[1i7u]], [[1jf1]], [[1jht]], [[1i4f]], [[1e27]], [[1e28]], [[1i1y]], [[1i1f]], [[1qqd]], [[1mhe]], [[1b0g]], [[1a9b]], [[1a9e]], [[1a1m]], [[1a1n]], [[1a1o]], [[1tmc]], [[2clr]], [[1hhg]], [[1hhh]], [[1hhi]], [[1hhj]], [[1hhk]], [[1hsb]], [[1hsa]], [[3to2]], [[2vab]] - hMHC I α + β-2-microglobulin + peptide<br />
**[[1ktl]], [[3kww]], [[3h9h]], [[3ixa]], [[3gso]], [[3gsq]], [[3gsr]], [[3gsu]], [[3gsv]], [[3gsw]], [[3gsx]], [[3ft2]], [[3ft3]], [[3ft4]], [[2av1]], [[2av7]], [[1cg9]], [[1m05]], [[1m6o]], [[1kpr]], [[1ktl]] - hMHC I α (mutant) + β-2-microglobulin + peptide<br />
**[[1syv]], [[1n2r]], [[1syv]] - hMHC I  + β-2-microglobulin + hMHC II peptide<br />
**[[1kjv]], [[1kjm]], [[1ed3]] – MHC I α + β-2-microglobulin + peptide - rat<br />
**[[2oi9]] - mMHC  I α + T cell receptor + peptide<br />
**[[1kbg]], [[3l3h]], [[3ftg]], [[3e6f]], [[3ecb]], [[3ch1]], [[3cch]], [[3cc5]], [[3cpl]], [[2zsv]], [[2zsw]], [[2zok]], [[2zol]], [[3buy]], [[2ve6]], [[2e7l]], [[2fo4]], [[2cii]], [[2fwo]], [[2f74]], [[1zt1]], [[1zt7]], [[1vgk]], [[1yn6]], [[1yn7]], [[1zhb]], [[1wbx]], [[1wby]], [[1wbz]], [[1rjy]], [[1rjz]], [[1rk0]], [[1rk1]], [[1t0m]], [[1t0n]], [[1s7q]], [[1s7r]], [[1s7s]], [[1s7t]], [[1s7u]], [[1s7v]], [[1s7w]], [[1s7x]], [[1lk2]], [[1kpu]], [[1kpv]], [[1n3n]], [[1nan]], [[1n59]], [[1n5a]], [[1ffn]], [[1ffo]], [[1ffp]], [[1g7p]], [[1g7q]], [[1lek]], [[1leg]], [[1inq]], [[1juf]], [[1k8d]], [[1jpf]], [[1jpg]], [[1fg2]], [[1qlf]], [[1bz9]], [[1kbg]], [[1hoc]], [[2mha]], [[1vad]], [[1vac]], [[3roo]], [[3quk]], [[3qul]], [[3rol]], [[3tbs]], [[3tbt]], [[3tbv]], [[3tbw]], [[4nsk]], [[3tby]] - mMHC  I + β-2-microglobulin + peptide<br />
**[[2qri]] - mMHC  I/β-2-microglobulin/peptide<br />
**[[2qrs]], [[2qrt]] - mMHC  I (mutant)/β-2-microglobulin/peptide<br />
**[[1mhc]], [[2clv]], [[2clz]], [[1fzj]], [[1fzk]], [[1fzm]], [[1fzo]], [[1ddh]] - mMHC  I (mutant) + β-2-microglobulin + peptide<br />
**[[3e2h]], [[3e3q]], [[2e7l]] - mMHC  I α (mutant) + T cell receptor + peptide<br />
**[[1nez]] - mMHC  I + β-2-microglobulin + CD8 α chain<br />
**[[3rwc]], [[3rwd]], [[3rwe]], [[3rwf]], [[3rwg]], [[3rwh]], [[3rwi]], [[3rwj]], [[4zfz]] - MHC  I + β-2-microglobulin + peptide – Rhesus macaque<br />
**[[3qq3]], [[3qq4]] - MHC  I + β-2-microglobulin + peptide - pig
 
*MHC I quaternary complex
 
**[[3qdg]], [[3qdj]], [[3qdm]], [[3qeq]], [[3mv7]], [[3mv9]], [[3h9s]], [[3gsn]], [[3d39]], [[3d3v]], [[3ffc]], [[2vlj]], [[2vlk]], [[2vll]], [[2vlr]], [[2j8u]], [[2p5e]], [[2p5w]], [[2pye]], [[2gj6]], [[2f54]], [[2esv]], [[2bnq]], [[2bnr]], [[1lp9]], [[1oga]], [[1mi5]], [[1qrn]] - hMHC  I α + T cell receptor + β-2-microglobulin + peptide<br />
**[[3kxf]], [[3mv8]], [[2jcc]], [[2uwe]] - hMHC  I α (mutant) + T cell receptor + β-2-microglobulin + peptide<br />
**[[2f53]] - hMHC  I α + T cell receptor + β-2-microglobulin (mutant) + peptide<br />
**[[1p7q]], [[1im9]] - hMHC  I α + leukocyte immunoglobulin-like receptor + β-2-microglobulin + peptide<br />
**[[2dyp]] - hMHC  I α (mutant) + leukocyte immunoglobulin-like receptor + β-2-microglobulin + peptide<br />
**[[3qzw]], [[3dmm]], [[1bqh]], [[1akj]] - hMHC I α + β-2-microglobulin + CD8 α + peptide<br />
**[[1im3]] - hMHC I α + β-2-microglobulin + cytomegalovirus protein US2 + peptide<br />
**[[3cii]], [[3cdg]] - hMHC I α + β-2-microglobulin + CD94 ectodomain + NKG2A/NKG2B integral membrane protein + peptide<br />
**[[3hae]], [[3gjf]], [[3cvh]], [[1w72]] - hMHC I α + β-2-microglobulin + antibody + peptide<br />
**[[1g6r]], [[2ckb]], [[3pqy]], [[2z31]], [[1nam]], [[1mwa]], [[1g6r]], [[2ckb]] - mMHC  I + T cell receptor + β-2-microglobulin + peptide<br />
**[[2oi9]] - mMHC  I (mutant) + T cell receptor + β-2-microglobulin + peptide<br />
**[[1p1z]], [[1p4l]], [[1qo3]] - mMHC  I + β-2-microglobulin + natural killer cell receptor LY49C + peptide<br />
**[[3c8k]] - mMHC  I (mutant) + β-2-microglobulin + natural killer cell receptor LY49C + peptide<br />
 
*'''MHC II'''
 
**[[3lqz]], [[2bc4]], [[1hdm]] - hMHC II α+β <br />
**[[3pdo]], [[3pgc]], [[3pgd]], [[1a6a]] - hMHC II α+β+γ<br />
**[[3cup]], [[2p24]], [[1lnu]], [[1fng]] - mMHC II α+β<br />
**[[1fne]] - mMHC II α+β (mutant) <br />
**[[3lqz]] - hMHC II α+β DP2
 
*MHC II binary complex
 
**[[1h15]] - hMHC II α+β + DNA polymerase peptide<br />
**[[1fv1]] - hMHC II α+β + myelin basic protein<br />
**[[3o6f]], [[2wbj]] - hMHC II α+β + T cell receptor<br />
**[[3l6f]], [[3c5j]], [[2q6w]], [[2fse]], [[1t5w]], [[1s9v]], [[1uvq]], [[1h15]], [[1fv1]] – hMHC II α+β + peptide<br />
**[[1dlh]] - hMHC II α+β + enterotoxin<br />
**[[3c5z]], [[3c60]], [[3c6l]] - mMHC II α+β + T cell receptor<br />
**[[1r5v]], [[1k2d]], [[1muj]], [[1kt2]], [[1ktd]], [[1f3j]], [[1es0]], [[1iak]], [[1iea]], [[1ieb]], [[1f3j]] - mMHC II α+β + peptide<br />
**[[1aqd]] - mMHC II α+β + MHC I peptide<br />
**[[1r5w]], [[1i3r]] - mMHC II α+β (mutant) + peptide<br />
 
*MHC II ternary complex
 
**[[1zgl]], [[1j8h]], [[1fyt]] - hMHC II α+β + T cell receptor + peptide<br />
**[[2iam]], [[2ian]], [[1ymm]], [[4gg6]] – hMHC II α+β + T cell receptor (mutant) + peptide<br />
**[[2ipk]], [[2g9h]], [[1pyw]], [[1jwm]], [[1jws]], [[1jwu]], [[1klg]], [[1klu]], [[1hxy]], [[1d5m]], [[1d5x]], [[1d5z]], [[1d6e]], [[2seb]], [[1seb]] - hMHC II α+β + enterotoxin + peptide<br />
**[[1sje]], [[1sjh]], [[1t5x]], [[1lo5]] - hMHC II α+β + enterotoxin (mutant) + peptide<br />
**[[1r5i]] - hMHC  II α+β + mycoplasma arthritidis mitogen+ peptide<br />
**[[2oje]] - mMHC  II α+β + mycoplasma arthritidis mitogen+ peptide<br />
**[[2xn9]], [[3qib]], [[1zgl]], [[3qiu]], [[3qiw]], [[3mbe]] - mMHC  I + T cell receptor + peptide<br />
**[[2pxy]], [[1u3h]] - mMHC II α+β + T cell receptor (mutant) + peptide<br />
**[[1jl4]] - mMHC II α+β + CD4 + peptide<br />
 
*MHC II quaternary complex


**[[2icw]] - mMHC  II α+β + T cell receptor + mycoplasma arthritidis mitogen + hemagglutinin peptide<br />
==See Also==
**[[4c56]] - hMHC  II + + T cell receptor + enterotoxin + hemagglutinin peptide<br />
* [[Major Histocompatibility Complex Class I]] which is about the history and impact of the first crystal structure.
}}
* A narrated YouTube video tutorial on MHC I and II (25 min) available at [http://molviz.org MolviZ.Org]
* [[Highest impact structures]]: 1987.


== References ==
== References ==

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Joel L. Sussman, Alexander Berchansky, Tihitina Y Aytenfisu, Eric Martz, Sandra B. Gabelli
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