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
MHC
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
MHC Class III
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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