Title: Major histocompatibility complex:
1Major histocompatibility complex Structure and
Function
Robert L. Ferris, MD, PhD Associate Professor,
Departments of Otolaryngology and of
Immunology Co-Leader, Immunology
Program University of Pittsburgh Cancer Institute
2Zinkernagel and Doherty
MHC restriction(Major Histocompatibility
Complex)
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8CD8 T cell, MHC-?2m-peptide
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13Image from Ian Wilson and co-workers
14Madden et al, Cell 1993
15MHC restriction(Major Histocompatibility
Complex)
16MHC restriction(Major Histocompatibility
Complex)
17Madden et al, Cell 1993
18Madden et al, Cell 1993
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23Figure 5.11
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25Figure 5.15
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28Figure 5.16
29Figure 5.16
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34Comparison of B cell and T cell antigen
receptors
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36Quantification of peptide specific T cells with
fluorescently labeled MHC-Class-I-complexes
Tetrameric MHC-Class-I-complex Tetramer loaded
with a peptide
A T cell receptor (TCR) binds to a tetramer in
the same way as to a MHC-class-I epitope
presented by a tumor cell
37Binding of tetramer was tested using anti-wt p53
CTL cell lines
CTL cell lines directed against anti-wt p53
epitopes
p53264-272
p5365-73
p53149-157
p53T149-157L
20
20
13
8
3x peptide stimulated
HLA-A2.1/p53264-272Tetramer
HLA-A2.1/p53149-157Tetramer
HLA-A2.1/p5365-73Tetramer
HLA-A2.1/p53149-157Tetramer
0.01
0.04
0.03
0.03
autologous unstimulated control
CD8
CD8
CD8
CD8
cell lines were generated from PBMC from patients
with head and neck cancer
38MHC allele associations with disease