MHC class II
MHC Class II | |
---|---|
Identifiers | |
Symbol | MHC Class II |
Membranome | 63 |
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional 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
Loading of a MHC class II molecule occurs by
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.
Mutations in the HLA gene complex can lead to bare lymphocyte syndrome (BLS), which is a type of MHC class II deficiency.
Structure
Like
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.
Expression
These molecules are constitutively expressed in professional, immune
MHC class II is also expressed on group 3 innate lymphoid cells.
Importance
Having MHC class II molecules present proper peptides that are bound stably is essential for overall immune function.
[5] 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 (CD4+). The peptide presented regulates how T cells respond to an infection.[5] Stable peptide binding is essential to prevent detachment and degradation of a peptide, which could occur without secure attachment to the MHC molecule.[5] This would prevent T cell recognition of the antigen, T cell recruitment, and a proper immune response.[5] The triggered appropriate immune response 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.
Synthesis
This section needs additional citations for verification. (June 2020) |
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
The invariant chain also facilitates the export of class II MHC from the ER to the
Recycling of MHC class II complexes
After MHC class II complexes are synthesized and presented on APCs they are unable to be expressed on the cell surface indefinitely, due to the internalization of the
Antigen processing and presentation
Unlike MHC I, MHC II is meant to present extracellular pathogens rather than intracellular. Furthermore, the first step is to acquire the pathogen through phagocytosis. The pathogen is then broken down in a lysosome and a desired component is then acquired and loaded onto a MHC II molecule. The MHC II molecule then travels to the surface to present the antigen to a helper T cell. MHC II active helper T cells which help release cytokines and other things which will help induce other cells which help to combat the pathogens outside the cells.
Genes
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 presentation
Pathway: PSD4–ARL14/ARF7–MYO1E
Molecules involved
Several molecules are involved in this pathway.[7]
- PIK3R2[8] and PIP5K1A[9] are two kinases that create substrates for PSD4.
- PSD4[10][11] (Pleckstrin and Sec7 Domain containing 4) is a GEF (Guanine nucleotide Exchange Factor) that loads ARL14/ARF7 with GTP.
- ARL14/ARF7[12] is a Small GTPase protein that is selectively expressed in immune cells. This protein is localized within MHC-II compartments in immature dendritic cells.
- ARF7EP[13] is an effector of ARL14/ARF7 that interacts with MYO1E.
- MYO1E[14] is a protein that controls MHC-II compartments with an actin-based mechanism.
Pathway
PIK3R2 and PIP5K1A are two
Bare lymphocyte syndrome
One type of MHC class II deficiency, also called bare lymphocyte syndrome, is due to mutations in the genes that code for transcription factors that regulate the expression of the MHC class II genes.
MHC class II and Type I diabetes
MHC class II genes and molecules are related to a multitude of different diseases, one of which being
See also
References
- ^ "Histocompatibility". Archived from the original on 2008-12-26. Retrieved 2009-01-21.
- S2CID 131777.
- PMID 11983150.
- ^ PMID 25720354.
- ^ OCLC 820117219.
- S2CID 8199773.
- PMID 21458045.
- ^ "PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 (beta) [Homo sapiens (human)]". Entrez Gene.
- ^ "PIP5K1A phosphatidylinositol-4-phosphate 5-kinase, type I, alpha [Homo sapiens (human)". Entrez Gene.
- ^ PSD4 pleckstrin and Sec7 domain containing 4 [Homo sapiens (human)] - Gene - NCBI
- PMID 14662749.
- ^ "ARL14 ADP-ribosylation factor-like 14 [Homo sapiens (human)". Entrez Gene.
- ^ "ARL14EP ADP-ribosylation factor-like 14 effector protein [Homo sapiens (human)". Entrez Gene.
- ^ "MYO1E myosin IE [Homo sapiens (human)". Entrez Gene.
- PMID 17513710.
- OCLC 986987876.
- PMID 17349258.
- S2CID 26085603.
External links
- Histocompatibility+Antigens+Class+II at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- MHC+Class+II+Genes at the U.S. National Library of Medicine Medical Subject Headings (MeSH)