Genetics of MHC and influence of polymorphism on function

1
Genetics of MHC and influence of polymorphism on
function Russell Salter February 7, 2007
2
(No Transcript)
3
(No Transcript)
4
Fig 5.11
5
Fig 5.12
6
Polygeny and Allelic Polymorphism
7
Fig 5.14
8
Haplotype A Haplotype B
Fig 5.15
9
Fig 5.13
10
Fig 5.16
11
Fig 5.17
12
Fig 5.19
13
Human MHC Nomenclature (HLA)
Class I Loci A,B,C Serologic definition A2,
B7, Cw3, etc Molecular definition A0201,
B0702, etc.
Class II Loci DR, DP, DQ Serologic
definition DR4, DQ3, DP1, etc Molecular
definition DRB10401, etc
14
Mouse MHC Nomenclature (H-2)
Class I Loci K, D, L Serologic definition
Kd, Db, Ld, etc. Molecular definition Kd, Dd,
Ld, etc
Class II Loci I-A, I-E Serologic definition
I-Ad, I-Eb, etc Molecular definition I-Ad,
I-Eb, etc
15
Autoimmunity
16
Fig 13.20
17
Fig 13.21
18
Fig 13.22
19
Asp57 forms a salt bridge to arg, stabilizing the
class II dimer (top panel)
Fig 13.23
20
Transplantation
21
Fig 13.38
22
Fig 5.18
23
Fig 13.42
24
Fig 13.37
25
Immunodeficiency
26
Bare Lymphocyte Syndrome

• Lack class II MHC on APC and thymus
• Few CD4 cells are present, mostly non-responsive
• Class I and CD8 T cells normal
• SCID (severe combined immunodeficiency)

27
Bare Lymphocyte Syndrome
28
Ting JP, Trowsdale J. Genetic control of MHC
class II expression. Cell. 2002 109
SupplS21-33.
29
Bare Lymphocyte Syndrome (class I MHC)

• Chronic Respiratory infections and skin
  ulcerations
• Very little surface class I MHC
• Normal mRNA for class I heavy chains and b2m
• Defect in TAP