IMM250H1 Study Guide - Final Guide: Mhc Class I, Histocompatibility, Cell-Mediated Immunity

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3 Feb 2013

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Major Histocompatibility Complex
Collection of genes involved in immune response
Usually clustered together on a single chromosome in jawed vertebrates
jawed means they have an adaptive immune system
o Humans = chromosome 6
o Mouse = chromosome 17
Histocompatibility: when cells of one tissue can survive in the presence of cells of another tissue
MHC genes originally isolated for their role in grafts / transplants
Mismatches in MHC alleles are what cause graft rejections
MHC restriction: T cells recognize peptide antigen only when it’s bound to a self-MHC molecule
MHC vs. HLA & H-2 same structure and fxn, different terminology
MHC = major histocompatibility complex genetic complex in all vertebrates
HLA = human leukocyte antigen name for human MHC
H-2 name for mouse MHC
Genes that code for associated immunological or antigen presenting molecules
Complement, interferon, tumor necrosis factor
Also contains many genes not related to immune fxn
Proteasome genes: breakdown of cytoplasmic proteins into peptides ()
o Recall: cylindrical garborator that destroys proteins tagged w/ ubiquitin
o Has MHC class I fxn b/c it chops up big proteins into smaller useful protiens
TAP: transporter associated with Antigen Processing
o Moves peptides into ER so that MHC class I molecules in ER can bind them
DMA + DMB: combine to make DM (MHC class II related molecule)
o Assists class II receptor in loading peptides
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MHC Class I
Involved in response to intracellular pathogens
A, B, C
Part of cellular immunity
Initiates CD8+ (killer) T cells
MHC Class II
Class II: Involved in response to extracellular
pathogens DR, DQ, DP
Part of humoral immunity
Initiates CD4+ (helper) T cells
MHC Class I and II
Immunoglobulin superfamily members
Has multiple gene copies lots of binding diversity lots of immune response diversity
Co-dominantly expressed: both mom + dad MHCs are expressed on surface
o Means there is a low probability for matching MHCs
Set of alleles (mom + dad) present on each chromosome
o Inherit MHC as haplotype (i.e. all genes are together on one chromosome)
Both mom + dad genes are highly polymorphic (many alleles in population)
Most polymorphic nuclear encoded genes
Means there are differences at the species level, not individual level
Need polymorphism b/c there are lots of pathogens out there!
Diff alleles have diff capacities for binding peptides
# of alleles in population = range of protection
MHC Class I and II alleles in humans
There are 3 Class I genes we have 2 alleles of each
o 2414 × 2728 × 2210 = 2 × 101352 possible combos of Class 1 alleles
For ~ 6 × 1010 ppl
o ABC is a combination that only you have that specifies “self”
esp. to your T cells
Actually less b/c of haplotypes, but we also have 3 of each Class II gene
Certain allele patterns are specific to different racial populations
o can use polymorphism to trace populations / lineage
MHC receptor structure
MHC Class I and II made up of 2 diff polypeptides (heterodimers) containing Ig domains
Like “heavy chain” of Ig
Both anchored in membrane
Both have a “groove” at distal end to hold antigen
MHC is not stable unless there is a protein in the groove
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