Major Histocompatability Complexes - Revision history

Bara at 16:19, 2 July 2012

2012-07-02T16:19:26Z

Rjfrancisrvc: /* MHC Polymorphism In People */

2012-05-24T09:56:11Z

MHC Polymorphism In People

Rjfrancisrvc: /* TCR-MHC Interaction */

2012-05-16T10:59:37Z

TCR-MHC Interaction

Rjfrancisrvc: /* TCR-MHC Interaction */

2012-05-16T10:57:22Z

TCR-MHC Interaction

Rjfrancisrvc: /* Presentation Pathway */

2012-05-16T10:55:14Z

Presentation Pathway

Rjfrancisrvc: /* Presentation Pathway */

2012-05-16T10:54:47Z

Presentation Pathway

Rjfrancisrvc: /* Presentation Pathway */

2012-05-16T10:51:57Z

Presentation Pathway

Rjfrancisrvc: /* Presentation Pathway */

2012-05-16T10:51:14Z

Presentation Pathway

Rjfrancisrvc: /* Structure */

2012-05-16T10:42:30Z

Structure

Rjfrancisrvc: /* Introduction */

2012-05-16T10:40:21Z

Introduction

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 [[Image:MHC.jpg|thumb|right|250px|Major Histocompatibility Complexes - B. Catchpole, RVC 2008]]
 ==Introduction==
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 <br><br>
 {{Jim Bee 2007}}
 [[Category:Adaptive Immune System]]
 [[Category:Lymphocytes]]
 [[Category:Image Review]]

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 ===MHC Polymorphism In People===
-* There are three types (loci) of MHC class I molecules known as human leukocyte antigen (HLA)- A, B, and C
+* There are three types (loci) of MHC class I molecules known as human leukocyte antigen (HLA) - A, B, and C
 * Equally there are three loci of MHC class II molecules - HLAs DP, DQ and DR
 In the entire human population there are only approximately 50 different variants (alleles) at each MHC class I and class II locus.
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 The variation within MHC class I is entirely based on the class I heavy chain (the β2m is invariant). The variation within MHC class II is mainly within the &beta; chains. Every individual has two alleles at each MHC locus inherited one from each parent. Any individual will therefore express two variants at most at each locus.
 This gives a maximum variability for an individual of:
-* 6 different variants of MHC class I (2 each of HLA- A, B and C)
+* 6 different variants of MHC class I (2 each of HLA - A, B and C)
-* 6 different variants of MHC class II (2 each of HLA- DP, DQ and DR)
+* 6 different variants of MHC class II (2 each of HLA - DP, DQ and DR)
 Many animal species have fewer loci than the human e.g. ruminants have no MHC class II DP.

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 Only peptide associated with MHC will interact with and activate [[T cells]]. T cells therefore cannot be directly activated by a peptide on a foreign organism.
-T cells will react against foreign MHC molecules and this is the basis of graft rejection
+T cells will react against foreign MHC molecules (e.g. from a different person) and this is the basis of graft rejection, for example in Heart transplants.
 ==MHC Genetics (Polymorphism)==

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 ==TCR-MHC Interaction==
 [[Image:MHC T cell Interaction.jpg|thumb|right|200px|Molecules of T lymphocyte recognition - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
-Only peptide associated with self-MHC will interact with and activate [[T cells]], which cannot be activated by a peptide on a foreign cell.
+Only peptide associated with MHC will interact with and activate [[T cells]]. T cells therefore cannot be directly activated by a peptide on a foreign organism.
 T cells will react against foreign MHC molecules and this is the basis of graft rejection

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 ===Presentation Pathway===
 [[Image:MHC I processing.jpg|thumb|200px|left|'''MHC I presentation pathway, courtesy of B. Catchpole, 2008''']]
-MHC I presents '''endogenous''' (intracellular) peptides. Viral proteins are broken down to peptides by the proteasome and transferred to the endoplasmic reticulum (ER) via transporters associated with antigen processing (TAP) molecules. In the ER peptides are processed with empty MHC I molecules and exported to the cell surface for presentation to the T-cell receptors of [[T_cells#Cytotoxic_CD8.2B|CD8<sup>+</sup> T-cells]]. The purpose of presentation in this manner is to kill the cell to prevent viral replication. Activation of the cell with Interferon enhances expression of MHC class I molecules as part of the [[Innate Immunity to Viruses|innate immunity]] to viruses.
+MHC I presents '''endogenous''' (intracellular) peptides. Viral proteins are broken down to peptides by the proteasome and transferred to the endoplasmic reticulum (ER) via transporters associated with antigen processing (TAP) molecules. In the ER peptides are processed with empty MHC I molecules and exported to the cell surface for presentation to the T-cell receptors of [[T_cells#Cytotoxic_CD8.2B|CD8<sup>+</sup> T-cells]]. The purpose of presentation in this manner is to kill the cell to prevent viral replication. Activation of the cell with '''Interferon''' enhances expression of MHC class I molecules as part of the [[Innate Immunity to Viruses|innate immunity]] to viruses.
 ==MHC II==

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 [[Image:MHC I Structure.jpg|thumb|right|200px| Structure of MHC I molecule - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
-MHC class I is expressed on virtually all nucleated cells and consists of a membrane-associated heavy chain bound non-covalently with a secreted light chain. The heavy chain is made up of three distinct extracellular protein domains - &alpha;1, &alpha;2 and &alpha;3. The heavy chain C - terminus is cytoplasmic.
+MHC class I is expressed on virtually all nucleated cells (so, for example, it is not expressed on erythrocytes), although quantity varies betweeen cell types, and consists of a membrane-associated heavy chain bound non-covalently with a secreted light chain. The heavy chain is made up of three distinct extracellular protein domains - &alpha;1, &alpha;2 and &alpha;3. The heavy chain C - terminus is cytoplasmic.
 The light chain is known as &beta;2-microglobulin and is similar in structure to one of the heavy chain domains. It is not membrane associated but binds to the α3-domain of the heavy chain.