1 Antigen Presentation and T Lymphocyte Activation Shiv Pillai MD, PhD Massachusetts General Hospital Harvard Medical School FOCiS
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
Why do we need T cells?
4 T cells ignore soluble shapes- only recognize billboards with peptides
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
# 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 7 14 200 Days after infection
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.
Secondary Lymphoid Organs- T and B cell zones B B T
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
Morphology of Dendritic Cells Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
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.
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
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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.
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.
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.
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.
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.
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.
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.
Activated T cells need to stay long enough in lymph nodes in order to complete the process 21
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The T cell receptor complex: associated proteins have cytoplasmic tyrosine based motifs called ITAMs 23
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.
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.
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.
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.
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
The Immunologic Synapse (2) Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2011 by Saunders, an imprint of Elsevier Inc.
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.
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.
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.
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.
Summary 34
Lord of the rings... 35