L4 - MHC and Antigen Recognition by T cells Flashcards
Thymus: what is it, where is it located, what does it do, and how does age affect its function?
the organ responsible for T-cell production
Behind sternum
Produces either CD4 (helper) T-cells or CD8 (cytotoxic) T-cells
Involutes (shrinks)
TCR: what is it, what chains are present, what regions are present and what do they do?
T-cell receptor
α and β chains
Variable region - contains hypervariable regions which allow for many different CDRs (complementary determining regions)
Constant region
Hinge region
Transmembrane region
Cytoplasmic tail
TCR vs BCR
Y shape vs II shape
T - signal transducing molecules are on both sides
B - only one side
BCR recognise “a part” of an antigen while TCR recognise antigenic peptides.
CD3: what is it, what does it do, and how does the CD3/TCR complex become activated?
A T-cell co-receptor that is not directly involved in antigen recognition but interacts with TCR to mediate intracellular signalling.
An early event in TCR activation is phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) on the cytosolic side of the TCR/CD3 complex by lymphocyte protein tyrosine kinase (Lck)
(link to lecture 9)
MHC: what is it, what does it do, how is it encoded, what is the form in humans and other animals, and what special features do they have?
Major histocompatibility complex
Act as antigen-presenting molecules - they bind antigenic peptides and present them on the surface of the cell
Coded by a collection of genes arrayed within a long continuous stretch of DNA.
HLA complex (Human Leukocyte Antigen), animals have different names for their MHC
Polygenic - several different class-I and class-2 genes
Polymorphic - various different forms within a population - due to co-dominance of the gene
MHC-I vs MHC-II: how many chains, where are they expressed, and what domains are present?
MHC-I:
* 3 α-chains bound by one transmembrane domain
* Present on most nucleated cells
* covalently linked to a 2β chain
MHC-II:
* 2α and 2β chains separately bound to the membrane that work closely but not covalently linked
* Restricted expression, e.g macrophages, B cells
* Both chains have transmembrane and cytoplasmic domains
MHC-I: what is it, what does it do, and how are its chains coded for?
Cell surface glycoproteins expressed on all nucleated cells - highly specialised antigen- presenting molecules that forms complexes with peptide ligands
Involved in T cell recognition of antigen (Tc).
- α-chain of MHC-I is encoded by the A, B & C loci in humans.
- β2-microglobulin is encoded by a gene in a different chromosome
MHC-II: what is it, what does it do, and how are its chains coded for?
Cell surface glycoproteins expressed on antigen-presenting cells (eg. Macrophages, dendritic cells and B-cells) - highly specialised antigen- presenting molecules that forms complexes with peptide ligands
Involved in T cell recognition of antigen (TH).
Encoded by the DP, DQ and DR regions in humans, encoding the α and β chains
MHC class III: what is it and what functions do they have?
Various proteins with or without immune function
- Components of complement
- Tumour necrosis factor
- Heat shock proteins
What size are the antigenic peptides of MHC-I and MHC-II and why are they this size>
MHC-I - 8-10(?)
MHC-II - >13(?)
Antigenic peptides are produced from proteins by a process called antigen processing to make small fragments (7-18 aa).
What type of antigens do MHC-I and MHC-II present?
MHC-I: involved in presentation of intracellular antigens - viral
MHC-II is involved in presentation of extracellular antigens - parasites, some bacteria
Processing of endogenous antigen to class I MHC: what is the process?
1 - Antigen is degraded in the proteosome
2 - Antigen peptides are transported to the rER by the transporter associated with antigen processing (TAP)
3 - p88 (calnexin) dissociates from MHC-I when a peptide binds (is this even true??? rewatch leccy)
4 - Fully folded MHC-I is exported
MHC-I folding: what is the process behind its complete folding?
1 - MHC-I α-chains bind to calnexin until the β-microglobulin part binds
2 - MHC-I complex dissociates from calnexin and associates with TAP and a complex of chaperone proteins (calreticulin and tapexin)
3 - TAP delivers a peptide received from the proteosome to the complex, causing it to complete its folding and export
Processing of exogenous antigen to class II MHC
1 - antigen taken up by endocytosis
2 - endosome and lysosome form the endolysosome
3 - enzymes in endolysosome degrade antigen
4 - Class-II MHC synthesised in RER with associated peptide-invariant chain
5 - Class-II MHC fuses with endolysosome
6 - invariant chain degraded and is displaced by antigen peptides of right size
7 - MHC/peptide complex transported to cell surface and present peptide
MHC-II activation: what is the process behind its complete activation?
1 - Invariant chain blocks binding of other proteins
2 - The class II-associated invariant chain peptide (CLIP) is then cleaved in an acidic environment but still bound
3 - CLIP prevents antigen peptide binding
4 - HLA-DM binds to MHC-II, dissociating it from CLIP and allowing other proteins to bind
5 - MHC-II then travels to the cell surface
