Week 7: Immunology III

MHC (Major histocompatibility complex)

This is the locus that encodes for a set of proteins essential for the adaptive immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility. The MHC determines compatibility of donors for organ transplant.

MHC molecules

Highly polymorphic cell surface proteins encoded by MHC class I and MHC class II genes involved in presenting peptide antigens to TCR of T cells

MHCI

Polymorphic cell surface proteins encoded by MHC locus and expressed on all nucleated cells. They present antigenic peptides generated in the cytosol to CD8 T cells and also bind the co-receptor CD8.

MHCII

Polymorphic cell surface proteins encoded by MHC locus and expressed on specialised antigen presenting cells. They present antigenic peptides derived from internalised extracellular pathogens (phagocytosed or endocytosed) to CD4 T cells and also bind the co-receptor CD4.

TAP1 and 2

(Transporters associated with Antigen Processing) Translocate peptides from cytosol into ER lumen.

HLA (Human Leukocyte Antigen) Complex

This is the name for the human MHC complex which is a locus encoding the human counterparts of MHC I and II proteins and other proteins involved in antigen presentation

HLA-A, -B, -C

These are the highly polymorphic human MHCI cell surface proteins found on all nucleated cells

HLA-DP, -DQ, -DR

These are the highly polymorphic human MHCII cell surface proteins found on antigen presenting cells.

HLA-DM

This is an HLA protein involved in loading peptides onto MHCII proteins (HLA-DP, -DQ, -DR).

Antigen presenting cells (APC)

These are cells that can process antigens and present their peptide fragments on MHCII on the cell surface. They are the dendritic cells, macrophages and B cells. They are involved in activating naïve T cells – mainly dendritic cells. The APCs present peptides to effector T cells and then get help to function more efficiently (dendritic cell, macrophage) or differentiated into a plasma cell (B cell).

Immunological synapse

The highly organised interaction between T cells and the activating or target cell it is in contact with. It is formed by TCR interacting with antigen on MHC and a second signal.

First signal

TCR and co receptor of T cell binding to antigen peptide on MHC.

Second signal

The signal needed to fully activate. It is between B7 on mature dendritic cells and CD28 on naïve T cells and CD40 on APCs and CD40L on effector CD4T cells.

Chemokine

Small chemoattractant protein that stimulates the migration and activation of cells particularly phagocytic cells and lymphocytes.

Jak (Janus Kinase)

A tyrosine kinase associated with the cytokine receptor, one with each monomer of the receptor. On ligand binding, each JAK phosphorylates the other, fully activating them and then they phosphorylate tyrosine amino acids in the cytokine receptor tail.

STAT (Signal transducers and activators of transcription)

A transcription factor that is phosphorylated by JAK and then can form active dimers that result in the transcription of genes.

Interferon (IFN)

A family of cytokines originally named for their interference of viral replication. IFNα and IFNβ are antiviral in their effects.

Interleukin (IL)

A generic name for cytokines produced by leukocytes.

Cytokine

Proteins made by cells that affect the behaviour of other cells particularly immune cells. The majority signal through the cytokine or JAK STAT pathway.

NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells)

A heterodimeric transcription factor activated by IL1, TLR, TNF, TCR and BCR signalling.

IκB (Inhibitor of NFκB)

A cytoplasmic protein that associates with NFκB and retains it in the cytoplasm. When IκB is phosphorylated by IKKβ, it is degraded by the proteasome and this allows the NFκB to be an active transcription factor.

IKK (Inhibitor of NFκB Kinase)

This is a kinase that phosphorylates IκB and results in its degradation.

TAK1

A serine threonine kinase that phosphorylates IKKβ and activates it

Rel homologous domain

A domain found in NFκB family of transcription factors that binds DNA.

TAD domain

Transactivation domain present in NFκB class II proteins is a transcription factor scaffold domain which contains biding sites for other proteins such as transcription co regulators and activates gene expression.