Chapter 3 Antigen Recognition by B-cell and T

Chapter 3 Antigen Recognition by B-cell and T

Murphy • Travers • Walport
Janeway’s Immunobiology:
Seventh Edition
Angewandte Immunologie
Chapter 3
Antigen Recognition by B-cell
and T-cell Receptors
Abt. Klinische Immunologie
Immo Prinz, Institute for Immunology
(Basic Immunology, MHH, K11)
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pepsin
pepsin
Henry Bence Jones
Jones HB (1848). "On a new
substance occurring in the urine of
a patient with mollities ossium".
Phil Trans R Soc Lond 138: 55–
62.
Paul Ehrlich
Term „Antikörper“
"Experimental Studies on Immunity",
published in October 1891
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Basic concept of adaptive immune
recognition
•
One B cell, one specificity.
•
•
„Auf jeden Topf passt ein Deckel.“
„Every pot has its lid.“
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Therapeutic antibodies
TCR resembles a Fab fragment
Palivizumab (Synagis)
RSV A-Epitope
Adalimumab (Humira)
Infliximab (Remicade)
Omalizumab (Xolair)
TNF-a
TNF-a
IgE
Natalizumab (Tysabri)
Efalizumab (Raptiva)
α4-Integrin
LFA-1
Bevacizumab (Avastin)
Cetuximab (Erbitux)
Trastuzumab (Herceptin)
VEGF
EGFR
HER2
Gemtuzumab Ozogamicin (Mylotarg)
Rituximab (Rituxan)
Alemtuzumab (Mabcampath)
CD33
CD20
CD52
Basiliximab and Daclizumab
CD25
Muromonab (Orthoclone)
CD3 (1986!!!)
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Structure of the TCR
TCR:CD3 complex
α
β
CD3
CD3
δ ε
γ ε
ITAM
www.biocarta.com
ITAM
ζ
ITAMs
ITAM: immunoreceptor tyrosin-based activation motif
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CD8 co-receptor
CD4 co-receptor
α
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β
α
β
CD4
CD3
CD3
δ ε
γ ε
ζ
Fyn
CD8
Lck
CD3
CD3
δ ε
γ ε
Lck
ζ
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MHC class I
Peptide binding to MHC-I
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Peptide presentation via MHC-I
MHC class II
Short peptides
(8 to 10 amino acids)
Hydrophobic AA
L: Leucine
V: Valine
I:
Isoleucine
β-sheet
Aromatic AA
Y: Tyrosine
F: Phenylalanine
α-helix
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Peptide binding to MHC-II
Peptide presentation via MHC-II
Peptide > 12 AA
Maus
Mouse MHC-II Ak
Human HLA-DR3
Alkalinic AA
K: Lysine
R: Arginine
H: Histidine
Q: Glutamine
N: Asparagine
Hydrophobic AA
L: Leucine
F: Phenylalanine
I: Isoleucine
Y: Tyrosin
Mensch
Negativly charged AA
D: Asparagine
E: Glutamine
1
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4
6
9
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Take home:
“T cells must deliver effector functions
appropriate to the cellular localization of
the pathogen / antigen”
“One T cell has one specificity”
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Murphy • Travers • Walport
Janeway’s Immunobiology:
Hozumi
and
Tonegawa
1976 PNAS
Seventh Edition
Angewandte Immunologie
Chapter 4
The Generation of Lymphocyte
Antigen Receptors
Abt. Klinische Immunologie
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GF
P
1:10,000 to 1:100,000
αβ T cells reinsert the
excised Tcrd circle!
=> Genomic instability.
One large transcript
immature
mature
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Maramatsu, ..., Honjo, T
Identification of AID as
cytidine deaminase.
Cell 2000, 102:553
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Murphy • Travers • Walport
Janeway’s Immunobiology:
Seventh Edition
Angewandte Immunologie
Chapter 5
Antigen Presentation to
T Lymphocytes
Abt. Klinische Immunologie
Basic Immunology
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Proc
Proc Biol
Biol Sci.
Sci. 1995
1995 Jun
Jun 22;260(1359):245-9.
22;260(1359):245-9.
MHC-dependent
MHC-dependent mate
mate preferences
preferences in
in humans.
humans.
Wedekind
Wedekind C,
C, Seebeck
Seebeck T,
T, Bettens
Bettens F,
F, Paepke
Paepke AJ.
AJ.
Abteilung
Abteilung Verhaltensökologie,
Verhaltensökologie, Universität
Universität Bern,
Bern,
Switzerland.
Switzerland.
Copyright
Copyright ©
© 2004
2004 Elsevier
Elsevier Inc.
Inc. All
All rights
rights reserved.
reserved.
New
New evidence
evidence that
that the
the MHC
MHC influences
influences odor
odor
perception
perception in
in humans:
humans: aa study
study with
with 58
58 Southern
Southern
Brazilian
Brazilian students
students
Pablo
Pablo Sandro
Sandro Carvalho
Carvalho Santos,
Santos, Juliano
Juliano Augusto
Augusto Schinemann,
Schinemann, Juarez
Juarez
Gabardo
Gabardo and
and Maria
Maria da
da Graça
Graça Bicalho
Bicalho,,LIGH—Laboratório
LIGH—Laboratório de
de
Imunogenética
Imunogenética ee Histocompatibilidade,
Histocompatibilidade, Departamento
Departamento de
de Genética,
Genética,
Setor
Setor de
de Ciências
Ciências Biológicas,
Biológicas, Centro
Centro Politécnico
Politécnico da
da Universidade
Universidade
Federal
Federal do
do Paraná,
Paraná, Jardim
Jardim das
das Américas,
Américas, Caixa
Caixa Postal
Postal 19071,
19071, CEP:
CEP:
81.530-990
81.530-990 Curitiba,
Curitiba, Paraná,
Paraná, Brazil
Brazil
Received
2
February
2004;
revised
1
June
2004;
accepted
Received 2 February 2004; revised 1 June 2004; accepted 55
November
November 2004.
2004.
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Take home
•
•
One lymphocyte, one specificity.
“T cells must deliver effector functions
appropriate to the cellular localization of the
pathogen / antigen” => MHC restriction
• Highest polymorphism found in MHC.
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