Beruflich Dokumente
Kultur Dokumente
Major Histocompatibility
Complex (MHC) and T Cell
Receptors
Riandini Aisyah
March 2010
System Biology
Historical Background
There were three kinds of molecules encoded by
the MHC
Class I
Class II
Class III
Historical Background
Nucleated cells
Class I MHC
RBCs
Class II MHC
APCs
Figure 3-19
Figure 5-11
2-microglobulin helps
stabilize the
conformation
Figure 5-13
Figure 5-16
LOGO
T cell activation
Figure 5-2
Figure 5-7
Figure 5-10
2003/11/26
System Biology
2003/11/26
System Biology
2003/11/26
System Biology
C00H
Ag peptide
Anchor
residue
Anchor site
MHC-II
MHC-IImolecule
molecule
V1
V2
D1
L Vn
J11--------J16
C1
D2 J11---------------J17
C2
E
D-J rearrangement
L
P
V1
V2
L Vn
D1J15 C1
D2 J11---------------J17
C2
V-D rearrangement
L
P
V1
P
C2
E
Transcription
V2 D1J15
C1
RNA
DNA
DNA
BCR (sIg)
Genes
TCR
Yes
Yes
VDJ rearrangement
Yes
Yes
Yes
Yes
Allelic exclusion
Yes
Yes
Somatic mutation
Yes
No
Transmembrane form
Yes
Yes
Secreted form
Yes
No
Yes
No
Proteins
Valence
Characteristics of interaction
1. Relative specificity
2. Flexibility
CD8+T cell(Tc)
CD4+T cell(Th)
T cell
Receptor
T cell
Receptor
Peptide
CD4
MHC
Class II
Peptide
CD8
MHC
Class I
Antigen Presenting
Cell
Antigen Presenting
Cell
Figure 5-17
Figure 5-18
Figure 5-20
MHC-Linked Diseases
Defects in MHC gene expression lead to
immunodeficiencies (MHC molecules are
required for both T cell development and
activation)
Some MHC alleles are associated with
susceptibility or resistance to autoimmune
diseases
MHC-Linked Immunodeficiencies
Bare Lymphocyte Syndromes lead to loss of MHC
molecule expression:
Defects in TAP genes prevent MHC Class I protein
surface expression (even though MHC proteins are
normal), so no CD8+ T cells - surprisingly mild
immunodeficiency (respiratory and skin infections)
Defects in TFs controlling Class II gene expression
(CIITA, RFXANK, RFX5, RFXAP) block CD4+ T cell
development - result in SCID (severe combined
immunodeficiency)
LOGO