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The Major Histocompatibility Complex

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Title: The Major Histocompatibility Complex


1
The Major HistocompatibilityComplex
  • Antigen Presentation and Processing
  • and the Relationship to
  • Susceptibility and Resistance to Diseases
  • Role of MHC in Tissue-Matching and
    Transplantation
  • HLA Typing in Sibling Matches Slides 45 46
  • (Supplemental Information, Not on Exam)

Folder Title MHC
Updated December 01, 2010
2
Factors and Immunogenicity 2
3
Factors and Immunogenicity 3
4
Antigens and MHC
5
Mixing Two Inbred Strain Haplotypes
p. 192
6
(No Transcript)
7
Mouse H2 Complex
Complement Proteins
Some Cytokines
Figure 8-1, Kuby 6th Edition, Top Half Human HLA
(Histocompatibility Complex), Lower Half Will Be
Discussed Later
8
H2 Haplotypes of some mouse strains
9
k and b Haplotype Team Members
See Table 7-1, Kuby 4th Edition, p. 175
10
Haplotype and Team Members
11
MLR Assay
See Figure 14-16, p.367, Kuby, 6th Edition
12
CML Assay
See Figure 14-17, Kuby 6th Edition, p. 368. For
CML Assay
See Figure 8-15, p. 207, Kuby, 6th Edition For
MHC Restriction. MHC Restriction will be covered
later
13
Restriction to Self MHC Alleles
14
This is a fill in the blank question. You should
already have your name transmitted so you should
get that string of letters and characters.If you
infected the mouse in the previous slide with
Influenza virus instead of LCM virus you would
not get Lysis of LCM-virus-infected self-cells.
What is missing from the spleen cells that are
used to test for lysis of LCM-virus-infected self
cells? What specific cells dont you have that
you need to get lysis?
15
(No Transcript)
16
MHC-I
See figure 8-3, Kuby, 6th Edition, p. 194, left
17
MHC-II
See figure 8-3, Kuby, 6th Edition, p. 194, right
18
Class I MHC Protein Binding Cleft
19
Ag Site Class I
See figure 8-4, Kuby, 6th Edition, p. 195, right
20
Ag-Bind
See figure 8-9(a,b), Kuby, 6th Edition, p. 199
21
(No Transcript)
22
Ag in Site Class I
See figure 8-9(c), Kuby, 6th Edition, p. 199
23
Class I MHC Space-Filling
24
H2K and Peptides
See figure 7-12, Kuby 4th edition, p. 184
25
MHC ClassI and Flu
26
MHC-Class I Polymorphisms
Kuby, 6th Edition Figure 8-10(b) p. 201 MHCIPoly
Positions of Polymorphic Amino Acid
Residues in a Human Class I MHC
Protein
27
Amino Acids Positions of Polymorphic Variations
in Class I MHC Proteins in Humans
Trans- Membrane Residues
Membrane Distal a1 and a2 Domains (Comprise
Peptide-binding Cleft)
Kuby, 6th Edition, Figure 8-10(a) p. 201
MHCIVary
28
MHC-II
See Figure 8-3, Right Kuby, 6h Edition p. 194
29
Class II MHC Space Filling
30
HMC-Class II Dimers
31
Comparison of Class I and Class II
32
TCR and MHC-Class II
33
MHC-Class II and Bound Antigen
34
Class I and Class II Antigen Acquisition
35
Variety of MHC Loci Allelles
See Figure 8-12, p. 203 Kuby, 6th Edition)
36
Presentation of Exo-Antigen (Class II)
See Figure 8-8, Kuby, 4th Edition, p. 209
37
(No Transcript)
38
Presentation of Endogenous Antigen (Class I )
See Figure 8-8, Kuby, 4th Edition, p. 209
39
You do not have to send in your name unless you
borrowed a BIO transmitter this morning. Make
sure your name is entered onto any borrowed
transmitter. What would happen to host response
to a virally infected cell if the virus shut-down
production of Class I MHC proteins?_____________
_______________________
40
You do not have to send in your name unless you
borrowed a BIO transmitter this morning. Make
sure your name is entered onto any borrowed
transmitter. The MHC gene complex is called the
Major Histocompatibility Complex because it
controlled the acceptance or rejection of __ ___
__ __ __ __ ___ __ __ __
41
Human HLA Loci
Class I Loci Equivalent toK, D, and L in Mice
Class II Loci Equivalent to IAa, IAb IEa, IEb in
Mice
Kuby, 6th Edition, Figure 8.01, Bottom Half
42
Polymorphism of Class I and Class II Molecules in
Human HLA
  • Humans 6 Different Class I Molecules
    HLA-A, HLA-B, HLA-C
  • (3 Class I from one parent, 3 from the other)
  • Approximate HLA Class I Alleles in Persons of
    European Descent
  • HLA-A 60 HLA-B 110 HLA-C
    40
  • Humans 12 Different Class II Molecules
    (Hetero-dimers) DPa,DPb, DQa,DQb, DRa, DRb
  • (6 Class II from one parent, 6 from the other)
  • Approximate HLA Class II Alleles in Persons of
    European Descent
  • 122 Alleles of HLA-DRbeta
    alone
  • Theoretical Combination of possible alleles is
    virtually infinite
  • Combination is inherited at birth
  • Does not diversify in an individual the way TCR
    or Antibodies do.
  • Diversity among individuals depends on degree of
    familial relationship
  • (full siblings histocompatible about 25 of
    the time)
  • Linkage Disequilibrium favors allele combinations
    based on (1) time of
  • divergence from population founder, (2)
    hot-spots facilitating genetic cross-overs,

MHCAlleles
43
  • Illustration of HLA
    Polymorphism,
  • Linkage Disequilibrium,and
    Tissue-Typing in Humans
  • Class I Loci
    Class II Loci
  • HLA-A HLA-B HLA-C DP DQ
    DR
  • 1 1 1 1 1 1
  • 2 2 2 2 2 2
  • 3 3 3 3 3 3
  • 4 4 4 4 4 4
  • 5 5 5 5 5 5
  • Example HLA-Types for Four
    Individuals
  • 2 4 1 5 2 4
  • 3 1 5 5 1 5
  • 2 4 1 3 1 2
  • 1 4 1 2 5 1

HLATyping
44
Association of Human MHC Alleles and Risk for
Diseases(from Table 7-4, Kuby Immunology, 4th
Edition, p. 193)
  • Disease Associated HLA Allele
    Relative Risk
  • Ankylosing Spondylitis B27
    90
  • Hereditary Hemochromatosis A3/B14
    90
  • Insulin Dependent Diabetes DR4/DR3
    20
  • Multiple Sclerosis DR2
    5
  • Myasthenia Gravis DR3
    10
  • Rheumatoid Arthritis DR4
    10
  • Systemic Lupus Erythromatosis DR3
    5
  • Narcolepsy DR2
    130
  • Autoimmune Disease Percent of Patients
    with Allele Divided by Percent of
    Non-Affected Persons with this Allele

See Table 7-4, Kuby 4th edition, p. 194
HLASick
45
You do not have to send in your name unless you
borrowed a BIO transmitter this morning. Make
sure your name is entered onto any borrowed
transmitter. The online streaming media videos
that you played on your own as a substitute for
the Nov. 22nd class was about the general subject
of Immunity to_________________________ disease.
46
Tissue-Typing Among SiblingsWhy Are Blood
Relatives More Likely to Be Compatible Donors?
  • Mom's Haplotypes (A,B,C, DP, DQ, DR) Dad's
    Haplotypes (A,B,C,DP, DQ, DR)
  • 1,2,3,4,5,6 7,8,9,10,11,12
    13,14,15,16,17,18 19,20,21,22,23,24

  • Children's Possible Haplotypes

  • Inherit from Mom
  • 1,2,3,4,5,6 1,2,3,4,5,6 7,8,9,10,11,12 7,8,9,
    10,11,12

  • Inherit from Dad
  • 13 to 18 19 to 24 13 to
    18 19 to 24
  • 25 of the Off-Spring
    Likely to be HLA Haplotypes
  • 1,2,3,4,5,6
    13,14,15,16,17,18
  • 1,2,3,4,5,6
    19,20,21,22,23,24
  • 7,8,9,10,11,12
    13,14,15,16,17,18
  • 7,8,9,10,11,12
    19,20,21,22,23,24

SibMatch
47
Tissue-Typing Among SiblingsWhy Are Blood
Relatives More Likely to Be Compatible
Donors?(SibMatch for Dummies version)
  • Mom's Parents (Nigel and Millicent)
    Dad's Parents (Duwayne and Loquida)
  • Nigel's Haplotypes Nigel W
    Duwayne's Haplotypes Duwayne Y
  • Millicent Haplotypes Millicent X
    Loquida's Haplotypes Loquida Z
  • Mom's Possible Haplotypes Dad's Possible
    Haplotypes
  • Nigel Millicent Duwayne Loquida
  • Nigel X Duwayne Z
  • W Millicent Y and
    Loquida
  • W X Y Z

  • Your Possible Haplotypes
  • Assume Your Mom got
    the Nigel Millicent Haplotypes
  • Assume Your Dad got
    the Duwayne Loquida Haplotypes
  • Inherit from Mom Nigel or Millicent
    Inherit from Dad Duwayne or Loquida
  • 25 of the
    Off-Spring Likely to be these Haplotypes

  • Nigel Duwayne

  • Nigel Loquida

  • Millicent Duwayne

  • Millicent Loquida

48
Mouse H2 Complex Detail
D Class I Locus
K
IA IB Major Class II Loci
Class I Locus
Figure 8-11, Kuby 6th Edition, p.202, (Selected
Part)
49
When this slide is opened be sure to use the
Send User Data directions to send in your name.
Remember to wait for the transmitter to go past
Presentation Mode Channel 41 In the previous
slide showing cells from the LCM virus challenged
mouse lysing LCM-infected self target cells What
will happen if the target cells are infected with
influenza virus?
  • Lysis
  • No Lysis

50
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Presentation Mode WAIT! Get Blank Screen Now
enter the number 1 for your response Get Your
answer 1A and a Check-mark Your receiver will
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