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Definition

Major histocompatibility complex (MHC) proteins are a group of highly polymorphic genes whose products appear on the surface of cells imparting the property of self (belonging to that organism). A genetic region found in all mammals whose products are primarily responsible for the rapid rejection of tissue grafts between individuals, and function in signaling between lymphocytes and cells expressing antigen.

Discovery

Discovery of the mouse MHC (H-2) - In 1916, Little and Tyzzer analyzed the fate of tumours transplanted between mice and demonstrated that several dominant genes influenced the outcome of allogenic tumour grafts1. The MHC was further characterized by Snell in transplantation studies in congenic mouse lines and he called the genes as histocompatibility (H) genes 2.

Discovery of the human MHC (HLA)-The human MHC is called the human leukocyte antigen (HLA) system and it was discovered from multiparous women or from transfused persons contained Abs which agglutinated leukocytes3. Initially, the serological typing techniques identified only two polymorphic gene loci, the HLA-A and HLA-B allelic series, but soon HLA-C and other gene loci in the MHC were identified 4.

Molecules related to MHC antigens, have been discovered. MHC class lb molecules are nonpolymorphic MHC class I-like molecules which fulfill functions divergent from the classical, MHC class la molecules. The human intestine is a unique immunologic compartment, which expresses two of these molecules: the neonatal Fc receptor for IgG (FcRn) and CDl5.

 

Structural Characteristics

The MHC genes, coding for the HLAs are located on the short arm of chromosome 6. Class I MHC is a heterodimer of membrane-bound a chain and non-covalently associated b2-microglobulin. Both ? chain and b2-microglobulin are members of the Ig superfamily and share with antibody, a disulfide-bonded domain structure. Class I? chain is encoded by highly polymorphic genes in the MHC. It has three domains named ?1, ?2, and ?3 and a region adjoining ?3 that anchors it in the plasma membrane. b2-microglobulin is encoded by a gene on another chromosome. b2-microglobulin molecules are non-covalently associated with Class Ia chain.

Class II MHC is a non-covalently bonded heterodimer of a and ß chains, called HLA-DP, HLA-DQ, and HLA-DR in humans and IA and IE in mice. Peptide antigen (13-18 residues) binds Class II a1 and ß1 domains, which are variable from allele to allele. a1 and ß1 domains also bind to T-cell receptors(TCR). The membrane-bound a2 and ß2 domains are invariant and a2 binds CD4. Class II peptide-binding site is similar in structure to that of Class I, except that its ends are more open so that longer peptides can be bound 6.

 

Mode of Action

MHC proteins must bind peptide, and Class I must be complexed with b2-microglobulin in intracellular compartments before MHC can be expressed on the cell surface. Peptide binding to MHC is less specific than epitope binding to Ig or TCR; each MHC presents many different epitopes. Peptide must bind MHC with enough affinity to be retained on the plasma membrane and not exchange with soluble peptide. For example, a virus-infected cell synthesizes virus proteins on ribosomes in its cytoplasm. In order to be presented, these proteins must be broken down into short peptides and transported into endoplasmic reticulum to bind to newly synthesized Class I MHC proteins. In the cytosolic processing pathway, cytosolic proteins are degraded to peptides in proteasomes, cylindrical arrays of proteolytic enzymes with their active sites towards the center of the cylinder. Both pathogen proteins and self cell proteins can be complexed with ubiquitin to target them to the proteasome for processing. Two proteases encoded in the MHC II region (LMP2 and LMP7) and a third subunit not encoded in MHC are produced in response to interferon, which is synthesized in response to virus infection. These inducible proteases replace constitutive proteases in the proteasome and produce peptides with basic and hydrophobic carboxyl terminal residues preferred as anchor residues in Class I peptide binding sites and for transport from the cytosol into the ER 7.

 

Functions

MHC proteins allow T cells to distinguish self from non-self. In every cell in the body, antigens are constantly broken up and presented to passing T cells. Without this presentation, other aspects of the immune response cannot occur. Class I MHC proteins present antigens to cytotoxic T lymphocytes (CTLs). Most CTLs possess both T-cell receptors (TCR) and CD8 molecules on their surfaces. These TCRs are able to recognize peptides when they are expressed in complexes with MHC Class I molecules. The TCR have a structure which allows it to bind the peptide-MHC complex. The accessory molecule CD8, bind to the alpha-3 domain of the MHC Class I molecule.

 

The MHC Class II proteins (found only on B lymphocytes, macrophages, and other cells that present antigens to T cells), primarily present peptides which have been digested from external sources and are needed for T-cell communication with B-cells and macrophages. Class II MHC proteins presenting antigens are detected by a different group of T cells (called T-helper or TH cells) to Class I MHC proteins (which are detected by CTLs cells) 7.

 

References

 

1.     Little CC, Tyzzer EE (1916). Further experimental studies on the inheritance of susceptibility to a transplantable tumor, carcinoma (JWA) of the Japanese waltzing mouse. J. Med. Res., 33:393-453.

2.     Snell GD (1948). Methods for the study of histocompatibility genes. J. Genet., 49:87-108.

3.     Payne  R, Rolfs MR (1958). Fetomaternal leukocyte incompatibility. J. Clin. Invest., 37(12):1756-1763.

4.     Bain B, Vaz MR, Lowenstein L (1964). The development of large immature mononuclear cells in mixed lymphocyte culture. Blood, 23:108-116.    

5.     Blumberg RS, Simister N, Christ AD, Israel EJ, Colgan SP, Balk SP (1996). MHC-like Molecules on Mucosal Epithelial Cells. Essentials of Mucosal Immunology, 8:85-99.

6.     Stern LJ, Wiley DC (1994). Antigenic peptide binding by class I and class II histocompatibility proteins. Structure, 2(4):245-51. Hughes AL, (1997). Molecular evolution of the vertebrate immune system. Bioessays, 19(9), 777-786.

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Product Name Catalog # Unit Price/Unit 
3Kp2, Class II MHC Molecule
ASFEAQKAKANKAVD
12537-01 1 mg $225 cart inquire
Adeno - Associated Virus Epitope 2 (AAV2)
VPQYGYLTL
12535-01 1 mg $120 cart inquire
α-gliadin (57–73)
QLQPFPQPELPYPQPQS
12524-01 1 mg $235 cart inquire
Apolipoprotein B - 100 (3136 - 3155), human
KTTKQSFDLSVKAQYKKNKH
12531-01 1 mg $270 cart inquire
BDC2.5 mimotope 1040 - 31
YVRPLWVRME
12542-01 1 mg $120 cart inquire
BDC2.5 mimotope 1040 - 51
RVLPLWVRME
12541-01 1 mg $215 cart inquire
CLIP(85-99)
KPVSQMRMATPLLMR
12522-01 1 mg $245 cart inquire
CLIP (86 - 100)
PVSKMRMATPLLMQA
12539-01 1 mg $225 cart inquire
CLIP (88-99)
SKMRMATPLLMQ
12538-01 1 mg $210 cart inquire
Eα (52–68)
ASFEAQGALANIAVDKA
12519-01 1 mg $120 cart inquire
EYK(EYA)3EYK
EYKEYAEYAEYAEYK
12527-01 1 mg $240 cart inquire
Glutamic Acid Decarboxylase (GAD65) (524 - 543) p524 - 543
SRLSKVAPVIKARMMEYGTT
14768-01 1 mg $116 cart inquire
HEL (46 - 61)
NTDGSTDYGILQINSR
12517-01 1 mg $138 cart inquire
IL - 8 Inhibitor
Ac-RRWWCR-CONH2
12532-01 1 mg $120 cart inquire
Immunodominant Mouse Minor Histocompatibility Anti
AAPDNRETF
12533-01 1 mg $210 cart inquire
LARFN5C (29 - 48), rat
PGPLQAKPFTILSPFLSSRC
12528-01 1 mg $250 cart inquire
LCMV (166 - 173), GP166
ITIQYNLT
12536-01 1 mg $225 cart inquire
LCMV (276 - 286) GP276
SGVENPGGYCL
14769-01 1 mg $120 cart inquire
LCMV gp33 - 41
KAVYNFATM
14770-01 1 mg $120 cart inquire
LLO190
NEKYAQAYPNVS
14771-01 1 mg $120 cart inquire
Mgp100 (25 - 33) mouse
EGSRNQDWL
14772-01 1 mg $120 cart inquire
MMK - 1, amide
LESIFRSLLFRVM-CONH2
12534-01 1 mg $220 cart inquire
Myelopeptide - 1 (MP - 1)
FLGFPT
12529-01 1 mg $205 cart inquire
Myelopeptide - 2 (MP - 2)
LVVYPW
12530-01 1 mg $210 cart inquire
NY - ESO - 1 (87 - 111)
LLEFYLAMPFATPMEAELARRSLAQ
12540-01 1 mg $193 cart inquire
p3K, (Lys 58 Lys 60 Lys 63) Ea(52–68)
ASFEAQKAKANKAVDKA
12520-01 1 mg $235 cart inquire
p3K truncated, (Lys 58 Lys 60 Lys 63) Ea(54–68)
FEAKGAKANKAVD
12521-01 1 mg $225 cart inquire
PIT (630–641), H+/K+ - ATPase alpha - Chain Peptid
PITAKAIAASVG
12525-01 1 mg $210 cart inquire
Plasmepsin V FRET Substrate
Dabcyl - LNKRLLHETQ - EDANS
14774-01 1 mg $188 cart inquire
Poly - γ - D - Glutamic Acid Construct
Ac - (γ - e)15 - C - NH2
14775-01 1 mg $176 cart inquire
Rnase (90–105)
SKYPNCAYKTTQANKH
12523-01 1 mg $245 cart inquire
Uty HY Peptide (246 - 254) mouse
WMHHNMDLI
14773-01 1 mg $120 cart inquire
VEGFR - 2/KDR II, murine
VILTNPISM
12526-01 1 mg $220 cart inquire
Vesicular Stomatitis Virus Nucleoprotein (52 - 59)
RGYVYQGL
12518-01 1 mg $215 cart inquire

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