Antigen Presentation and T Lymphocyte Activation. Shiv Pillai MD, PhD Massachusetts General Hospital Harvard Medical School. FOCiS
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1 1 Antigen Presentation and T Lymphocyte Activation Shiv Pillai MD, PhD Massachusetts General Hospital Harvard Medical School FOCiS
2 2 Lecture outline Overview of T cell activation and the rules of adaptive immunity The T cell receptor and what it sees Antigen Presentation Costimulation TCR signaling Calcium signaling and cyclosporin A Integration and Summary
3 Why do we need T cells?
4 4 T cells ignore soluble shapes- only recognize billboards with peptides
5 The rules of adaptive immunity from a T cell point of view Developing T cells mature and are tolerized in the thymusthe central lymphoid organ for the T lineage 5 Naïve T cells home to secondary lymphoid organs (SLOs - mainly lymph nodes) in search of antigens T cells require two signals for activation (occurs in SLOs) and develop into effector and memory cells Effector T cells migrate out of SLOs to sites of infection Eradication of infection and Contraction of Effectors
6 # of microbe-specific T cells T cell expansion and contraction (decline) 6 Clonal expansion 10 6 Contraction (homeostasis) 10 4 CD8 cells CD4 cells Memory 10 2 Infection Days after infection
7 Two cellular compartments- two MHC molecules-two T cells Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
8 Secondary Lymphoid Organs- T and B cell zones B B T
9 A Third Type of Sentinel Cell Initiates Adaptive Immunity Copyright 2011 by Saunders, an imprintof of Elsevier Inc. Inc. Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint Elsevier
10 Morphology of Dendritic Cells Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
11 DC Antigen Capture and Presentation Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
12 DCs and antigen find specific Naïve T cells in SLOs in the T cell zone: activated Effector T cells return to the site of infection 12
13 13
14 T cell Recognition of Peptide-MHC Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
15 Structure of a Class I MHC Molecule Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
16 Structure of a Class II MHC Molecule Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
17 Peptide Binding to MHC Molecules Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
18 Polymorphic Residues of MHC Molecules Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
19 Class I MHC Pathway of Antigen Presentation Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
20 Class II Pathway of Antigen Presentation Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
21 Activated T cells need to stay long enough in lymph nodes in order to complete the process 21
22 22
23 The T cell receptor complex: associated proteins have cytoplasmic tyrosine based motifs called ITAMs 23
24 Ligand-Receptor Pairs in T cell activation (1) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
25 Early Signaling Events in T cell Activation (1) Fig. 7-10a Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
26 Early Signaling Events in T cell Activation (2) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Copyright Saunders, 2011 by Saunders, an imprint an imprint of of Elsevier Inc. Inc.
27 Early Signaling Events in T cell Activation (3) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
28 The Immunologic Synapse (1) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 Copyright by Saunders, 2011 by Saunders, an imprint an of Elsevier Inc. Inc
29 The Immunologic Synapse (2) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
30 T cell Signaling Downstream of PLCg1 (1) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
31 T cell Signaling Downstream of PLCg1 (2) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
32 T cell Signaling Downstream of PLCg1 (3) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 Copyright by Saunders, 2011 by Saunders, an an imprint of of Elsevier Inc. Inc.
33 Activation of Transcription Factors in T Cells Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, Copyright 2011 an by Saunders, imprint an imprint of Elsevier of Inc.
34 Summary 34
35 Lord of the rings... 35
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