Bioms: Antigen Presentation & Histocompatibility

Front 1

What do T cell recognize?

Back 1

1. Antigens that have been processed by APC
2. antigen processing is necessary for T cell activation

Front 2

APC

Back 2

1. antigen presenting cells
2. generate fragments of antigen that associate with class I or class II proteins

Front 3

professional APC

Back 3

1. cells that can activate an immune response by presenting antigen to T cells
2. Dendritic cells, macrophages, B lymphocytes

Front 4

classes of T lymphocytes

Back 4

1. T helper cells (CD4+)
2. T cytotoxic cells (CD*+)

Front 5

CD4+ Th lymphocytes

Back 5

recognize antigen presented by class II proteins

Front 6

CD8+ Tc lymphocytes

Back 6

1. recognize antigen presented by class I proteins
2. bind to alpha-3 domain

Front 7

MCH class I

Back 7

1. present antigen of intracellular (endogenous) origin to CD8+
2. dimer of alpha chain and beta-2 microglobulin
3. peptide binding only by alpha chain (alpha-3)
4. has closed ends of the peptide binding groove
5. binds shorter peptides
6. peptides bound adopt different conformations (anchored at ends of peptide)
6. polygenic and polymorphic
7. present peptides via specific binding

Front 8

MCH class I presentation mechanism

Back 8

1. virus infects cell
2. viral proteins synthesized in cytoplasm
3. peptide fragments of viral proteins bound by MHC class I in ER
4. bound peptides transported by MHC class I to the cell surface
5. cytotoxic T cells (CD8+) recognize complex of viral peptide with MHC class I and kills infected cells

Front 9

MCH class II presentation mechanism

Back 9

1. macrophage engulfs and degrades bacterium producing peptides
2. bacterial peptides bound by MHC class II in vesicles
3. bound peptides transported by MHC class II to the cell surface
4. Helper T cell (CD4+) recognize complex of peptide antigen with MHC II and activates macrophage

Front 10

MCH class II

Back 10

1. present antigen of extracellular (exogenous) origin to CD4+
2. dimer of an alpha chain and a beta chain
3. peptide binding by both alpha and beta chain (Beta-2 domain)
4. open ends allow binding of longer peptides
5. anchored along peptide; constant elevation (no bulge like in class I)
6. polygenic and polymorphic
7. present peptides via specific binding

Front 11

Peptide binding by class I (mechanism)

Back 11

1. class I heavy chain stabilized by calnexin until B2-microglobulin binds
2. Calnexin released
3. heterodimer of class I heavy chain and B2m forms peptide-loading complex with calreticulin, tapasin, TAP, ERP57, AND PDI
3. peptide from TAP binds to class I heavy chain forming mature MHC class I molecule
4. class I molecule disassociates from peptide-loading complex
5. exported from ER

Front 12

Peptide binding by class II

Back 12

1. invariant chain blocks binding of peptides to MHC class II molecule in ER
2. Invariant chain cleaved (in vesicles) leaving CLIP fragment bound
3. CLIP blocks binding of peptides to MHC class II in vesicles
4. HLA-DM facilitates release of CLIP, allowing peptides to bind

Front 13

T cell receptors (TCR)

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bind both peptide and MHC

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Human leukocyte antigen (HLA)

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1. located on chromosome 6

Front 15

polymorphism

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1. there are many different alleles fro each MHC
2. analogous to the complement determining region of TCR and BCR
3. location of variability leads to binding of different sets of peptides

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polygenic

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1. several genes encode the same protein
2. genes have been duplicated

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haplotype

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how class I and class II genes are inherited (are close together in genome)

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Class I & II have diversity because?

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1. polygenic
2. polymorphic
3. co-dominantly expressed

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co dominance

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genes inherited from each parent are expressed

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why is diversity good for the individual?

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because chances are good that a peptide will find a class I or II to present it

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population

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because chances are good that at least some members of a species will be able to present an antigen