MHC class II


MHC class II molecules are a class of major histocompatibility complex MHC molecules normally found only on antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells These cells are important in initiating immune responses

The antigens presented by class II peptides are derived from extracellular proteins not cytosolic as in MHC class I

Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface

In humans, the MHC class II protein complex is encoded by the human leukocyte antigen gene complex HLA HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR

Contents

  • 1 Structure
  • 2 Expression
  • 3 Reaction to bacteria
  • 4 Synthesis
  • 5 Genes
  • 6 Pathways controlling MHC class II antigen presentation
    • 61 Pathway: PSD4 - ARL14/ARF7 - MYO1E
      • 611 Molecules involved
      • 612 Pathway
  • 7 See also
  • 8 References
  • 9 External links

Structureedit

Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC1 The subdesignation α1, α2, etc refers to separate domains within the HLA gene; each domain is usually encoded by a different exon within the gene, and some genes have further domains that encode leader sequences, transmembrane sequences, etc

Because the antigen-binding groove of MHC class II molecules is open at both ends while the corresponding groove on class I molecules is closed at each end, the antigens presented by MHC class II molecules are longer, generally between 15 and 24 amino acid residues long

Expressionedit

These molecules are constitutively expressed in professional, immune antigen presenting cells, but may also be induced on other cells by interferon γ2

MHC class II is also expressed on group 3 innate lymphoid cells

Reaction to bacteriaedit

Because class II MHC is loaded with extracellular proteins, it is mainly concerned with presentation of extracellular pathogens for example, bacteria that might be infecting a wound or the blood Class II molecules interact mainly with immune cells, like the T helper cell TCD4+ The helper T cells then help to trigger an appropriate immune response which may include localized inflammation and swelling due to recruitment of phagocytes or may lead to a full-force antibody immune response due to activation of B cells

Synthesisedit

During synthesis of class II MHC in the endoplasmic reticulum, the α and β chains are produced and complexed with a special polypeptide known as the invariant chain The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain Ii; a trimer to prevent it from binding cellular peptides or peptides from the endogenous pathway such as those that would be loaded onto class I MHC

The invariant chain also facilitates the export of class II MHC from the ER to the golgi, followed by fusion with a late endosome containing endocytosed, degraded proteins The invariant chain is then broken down in stages by proteases called cathepsins, leaving only a small fragment known as CLIP which maintains blockage of the peptide binding cleft on the MHC molecule An MHC class II-like structure, HLA-DM, facilitates CLIP removal and allows the binding of peptides with higher affinities The stable class II MHC is then presented on the cell surface

Genesedit

Alpha Beta
HLA-DM HLA-DMA HLA-DMB
HLA-DO HLA-DOA HLA-DOB
HLA-DP HLA-DPA1 HLA-DPB1
HLA-DQ HLA-DQA1, HLA-DQA2 HLA-DQB1, HLA-DQB2
HLA-DR HLA-DRA HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5

Pathways controlling MHC class II antigen presentationedit

Pathway: PSD4 - ARL14/ARF7 - MYO1Eedit

Molecules involvededit

Several molecules are involved in this pathway3

- PIK3R24 and PIP5K1A5 are two kinases that create substrates for PSD4

- PSD467 Pleckstrin and Sec7 Domain containing 4 is a GEF Guanine Exchange Factor that loads ARL14/ARF7 with GTP

- ARL14/ARF78 is a Small GTPase protein that is selectively expressed in immune cells This protein is localized within MCH-II compartments in immature Dendritic Cells

- ARF7EP9 is an effector of ARL14/ARF7 that interacts with MYO1E

- MYO1E10 is a protein that controls MHC-II compartments with an actin-based mechanism

Pathwayedit

PIK3R2 and PIP5K1A are two Kinases that phosphorylate Phosphatidylinositol PIP providing PSD4 with substrates for its GTP loading ability PSD4 as a Guanine Exchange Factor, loads ARL14/ARF7 with GTP Subsequently, ARF7EP interacts with MYO1E which binds itself to Actin myofibers Altogether, this complex contributes to maintain MHC-II loaded vesicles within the Immature Dendritic Cell, impeding its translocation to the cell membrane

Pathway showing how MHC-II distribution is controlled within Immature Dendritic Cells

See alsoedit

  • Cross-presentation

Referencesedit

  1. ^ "Histocompatibility" Retrieved 2009-01-21 
  2. ^ Ting, JP; Trowsdale, J Apr 2002 "Genetic control of MHC class II expression" Cell 109 Suppl: S21–33 PMID 11983150 doi:101016/s0092-86740200696-7 
  3. ^ Paul, P; van den Hoorn, T; Jongsma, ML; Bakker, MJ; Hengeveld, R; Janssen, L; Cresswell, P; Egan, DA; van Ham, M; Ten Brinke, A; Ovaa, H; Beijersbergen, RL; Kuijl, C; Neefjes, J 2011 "A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation" Cell 145 2: 268–83 PMID 21458045 doi:101016/jcell201103023 
  4. ^ PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 beta Homo sapiens human - Gene - NCBI
  5. ^ PIP5K1A phosphatidylinositol-4-phosphate 5-kinase, type I, alpha Homo sapiens human - Gene - NCBI
  6. ^ PSD4 pleckstrin and Sec7 domain containing 4 Homo sapiens human - Gene - NCBI
  7. ^ Prigent, M; Dubois, T; Raposo, G; et al 2003 "ARF6 controls post-endocytic recycling through its downstream exocyst complex effector" J Cell Biol 163 5: 1111–21 PMC 2173613  PMID 14662749 doi:101083/jcb200305029 CS1 maint: Explicit use of et al link
  8. ^ ARL14 ADP-ribosylation factor-like 14 Homo sapiens human - Gene - NCBI
  9. ^ ARL14EP ADP-ribosylation factor-like 14 effector protein Homo sapiens human - Gene - NCBI
  10. ^ MYO1E myosin IE Homo sapiens human - Gene - NCBI

External linksedit

  • Histocompatibility Antigens Class II at the US National Library of Medicine Medical Subject Headings MeSH
  • MHC Class II Genes at the US National Library of Medicine Medical Subject Headings MeSH


MHC class II Information about

MHC class II

MHC class II
MHC class II

MHC class II Information Video


MHC class II viewing the topic.
MHC class II what, MHC class II who, MHC class II explanation

There are excerpts from wikipedia on this article and video