Ch' 8' The Major Histocompatibility Complex

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Ch. 8. The Major Histocompatibility Complex
and Antigen Presentation Generation of T cell
responses Antigen processing and
presentation Development of T and B
cells Control of B cell response by T
cells Cell-mediated immunity
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T cell antigens are processed and presented
by MHC molecules (p. 82)
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All mammalian species have a MHC major
histocompatibility complex tightly linked
cluster of genes gene products are cell-surface
proteins involved in cell-cell
interaction antigen presentation recognition
of self-nonself molecules Humans- HLA complex
(human leukocyte antigen) Mice- H-2
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Three classes of MHC molecules Class I- almost
all nucleated cells antigen presentation to
cytotoxic T cells Class II- on
antigen-presenting cells antigen presentation to
helper T cells These molecules are cell-surface
glycoproteins Class III- secreted
proteins complement components inflammation
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Organization of the MHC (p. 190)
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Each locus is polymorphic Each set of alleles on
one chromosome is called a haplotype They are
expressed codominantly you get one haplotype
from each parent both are expressed on the cell
surface (All nucleated cells express MHC Class
I) APCs express both Class I and Class II
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Skin graft acceptance is controlled by MHC
p. 176
p. 192
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p. 192
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A widely used experimental system is
mouse strains Syngeneic strains- identical at
all (H-2) loci (e.g., BALB/c, DBA/2,
NZB) Congenic- identical except at a single
locus Strains were produced with careful
breeding over many generations
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What do the MHC molecules look like?
p. 194
Class II
Class I
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Three-dimensional structure of human Class I
p. 195
p. 195
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MHC molecules bind peptides. Binding sites
and the nature of the peptides is slightly
different.
p. 197
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MHC molecules are very polymorphic Not due to
gene rearrangement, like B and T cells but
multiple alleles. Alleles vary quite a
bit. Since there is so much polymorphism at each
of the several loci, the theoretical degree of
diversity is huge.
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Significance of polymorphism? Immune
responsiveness is determined by MHC Class II
haplotype (MHC restriction)
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Possible explanations

• Different MHC class II molecules differ in their
• ability to bind antigen

2. T cells may not recognize certain MHC- peptide
combinations, because they resemble self-antigen
too closely. These forbidden clones were
eliminated during development, resulting in a
hole in the repertoire.
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From Kuby, 5th edition
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Linkage disequilibium an association between
some MHC alleles and some diseases Complex
interaction between genes and the environment
(e.g., ID twins) May result from altered Ag
presentation or lack of TCRs to recognize
processed Ag Some MHC molecules may mimic
receptors for pathogens or their
toxins Reduction in polymorphism may predispose
species toward disease (e.g., cheetahs)