lecture 1-2 Flashcards

Question

T cells recognize peptides bound to what type of molecules?

Answer 1

T cells recognize peptides bound to two different classes of MHC molecules T cell will only recognise antigens presented out to them MHC1 (all cells in our body express MHC1 and can signal to T cells) - CD8 positive T cells (cytotoxic T cells, will see antigen presenting via our MHC1 signalling) - CD4 positive T cells (helper T cells, 2 transmembrane anchors in MHC2, will show antigenic peptides to CD4+ T cells)

Answer 2

TC cells orchestrate cell-mediated immunity during intracellular virus infections cytotoxic T cells important in viral infected cells virus is intracellular, broken down, shown on MHC1, cytotoxic T cell will see it and will kill the cell all cells can show its viral infection via MHC1

Answer 3

only certain cells express the MHC2 and they tend to be the antigen presenting cells (which have to be able to go through phagocytosis or receptor mediated endocytosis) because T helper cell can only see the exterior of an infected cell macrophage - takes in mycobacterium, breaks it down, shows it via MHC2, CD4+ T helper cells binds to it

Answer 4

LEARN THIS STRUCTURE IN L2 S2 antigen binds to the B cell receptors once the B cell is sure of what antigen it is, it is activated and will secrete receptors as immunoglobulin/antibody a domain is a functional part of the protein and it is usually conserved. they independently fold to give their independent functions so the domain of the polypeptide chain have different roles → so we have heavy chains and light chains / each have variable domains and constant domains disulfide bond forms a hinge, so it’s flexible

Answer 5

Both chains have constant and variable domains with a characteristic folded structure – 7-10 β strands linked via disulphide bond (Immunoglobulin fold)

Answer 6

we stretched out the polypeptide chain and number the residues of the primary sequence up to 120 look at many variations of these polypeptide chains look at the variations of these amino acids we find that at specific locations of this chain we get a real increase in diversity of these amino acids this gives us a unique pattern to the one specific immuno B cell receptor (like a fingerprint) these are called complementarity determining regions - CDRs OR hypovariable regions HR

Answer 7

Ag -can bind in pockets, grooves or extended surfaces in the binding site of the BCR and antibodies, but recognition is always of 3D shape

Answer 8

DIAGRAMS IN L2 S7

Answer 9

- T cell receptor resembles a membrane bound Fab fragment. Also has regions of hypervariablility (CDRs) - But is encoded by a completely different set of gene segments T cell receptor similar to FAB fragments of B cell receptors also part of the immunoglobulin super family so has immunoglobulin folds within the domains they are heterodimers because they have an alpha chain and a beta chain they have a constant region and variable region have 3 regions of each of the variable domains that allow for specificity and diversity similar so genes are similar but are still on different chromosomes

Answer 10

The T cell receptor is a heterodimeric membrane bound receptor have carbohydrates - help stabilise the molecule they have very short cytoplasmic tails which means it is not very good at signalling so will need help

Answer 11

overall response first T cell receptor has to recognise linear peptide of antigen B cell receptor will recognise 3D shapes if we want a b cell response, the t cells have to recognise it first to give the b cells a helping hand, to then produce its antibodies and immunoglobulins have to recognise the same source of pathogen, but in diff ways b-cell epitopes have different parts of the protein t-cell receptor has the fragments of that peptide chain the B cells can internalize it and present it to the T cell

Answer 12

TCR can only see its cognate AG if it is presented by a specific MHC molecule KNOW THE STRUCTURES AND ORDERS OF ALPHA DOMAINS MHC1 has 1 transmembrane domain which is composed of alpha 1 2 and 3 we also have a separate molecule because it is a different polypeptide chain called beta 2 microglobulin when b2 binds it provides stability looking at it from above we can see a binding groove formed by the alpha helix at the top and the Beta sheets at the bottom MHC2 has two transmembrane domains composed of alpha 1 and 2 and beta 1 and 2 so mhc1 and mhc2 are different and show different peptides to different types of T cells MHC1 - CYTOTOXIC T CELLS - CD8+ MHC2 - HELPER T CELLS - CD4+

Answer 13

These proteins stabilise the binding of TCR to the MHC:peptide complex. CD4 – a single molecule. CD8 either a heterodimer or homodimer. CD - cluster differentiation - a way to describe a protocol to look at expression on the surface CD4 - presented on a T helper cell. it has four domains on one polypeptide chain CD8 - presented on a T cytotoxic cell, is a heterodimer or a homodimer (so can have alpha alpha or beta beta). have a longer cytoplasmic tail to penetrate into the cytoplasm stabilise the interaction between T cell receptor and MHC play a role in signalling long cytoplasmic tail

Answer 14

The binding sites for CD4 and CD8 on the MHC II and MHCI respectively are on the immunoglobulin domains. close association of all proteins CD8+ cell - closely associated to the domains of our MHC1 molecules signals allow us to regulate and make sure we reached a threshold to get a good response from the activation of our T cells

Answer 15

MHC1 - binding groove will hold the polypeptide chain at both ends by ionic forces, hydrogen bonds peptide is a smaller the peptide needs to buldge out this there is some interaction between the side chain of the peptide chain and the side chain of the amino acid alpha helix and underneath on the Beta sheet groove closed off at the ends MHC2 - groove is more open so we can have a longer peptide chain mhc molecules are highly variable similarities in siblings, but not identical highly polygenic and polymorphic (variations across populations and between cells)

Answer 16

T cell receptors come down from the top interacts with the MHC molecule itself (grey) and the peptide (yellow) important to the T cell to recognise all of the potential repertoire of all the antigenic peptides and recognise the mhc molecules themselves to create strong interactions 1a and 2a focus on the carboxyl end of the mhc groove 2B and 1B focus on the amino end 3rd hypervariable region on both the alpha and beta chains js in close association with the peptide 3rd hypervariable region has to be the one that is the most diverse because it is the region that will recognise the antigen

Answer 17

The MHC molecule interacts with the peptide backbone via hydrogen bonds and ionic interactions (blue dots). Peptide ~8-10 aa in length alpha helices are creating the grooves and the Beta sheets are creating the floor of that binding groove specific anchor residues will incur the peptide chain into that binding group on the sides we find tyrosine residues which will bind to the amino side of the peptide chain, and some on the other side that will bind to the carboxyl side of the peptide chain have anchors residues on each side so peptide can buldge out and be a bit bigger COMMON TO ALL MHC1 if I take mhc-1 from all different types, and flush out the peptides there will be similarities

Answer 18

The MHC molecule interacts with the peptide backbone via hydrogen bonds and ionic interactions (blue dots) Peptide size is less constrained ~13-17 aa. this also happens in our mhc II molecules anchor residues are seen as the hydrogen bonds in blue diff MHC2 compared to MHC1 - not bound on the ends, just along the peptide chain, ends are hanging out a bit they are harder to identify anchor residues

Answer 19

TABLE IN L2 S21

Answer 20

1. Combinatorial diversity during segment recombination. [ when you look at the gene that codes for the B line receptor it is segmented (split into segments). so you get a random assortment of those segments so every B cell receptor will be different ] 2. Junctional diversity during segment joining. [ when you join these different segments together you adding new nucleotides at the junction of those segments which gives us junctional diversity. both give us difference amino acid primary sequences and so different diversities in that b-cell repertoire ] 3. Combinatorial diversity driven by different combinations of heavy and light chain. 4. Somatic hypermutation

Answer 21

Variable region genes are constructed from somatic recombination of separate gene segments in L chain - we have one recombination event in H chain - we have two recombination event ``` gene segments: V - variable gene segment J - joining C - constant gene segment L - leader sequence ``` so the diversity of the variable region of a light chain is a result of one type of V region binding to one type of J region. you can get shuffling of the gene segments from V and J regions - RANDOM this also happens in the heavy chain but twice because they have an extra gene segment called the diversity segment they have the variable, diverse and joining segments they start off with the shuffling of the segments for the heavy chain the first recombination event occurs when a D and a J join together the second recombination event is one of the types of V regents binding to one type of DJ combination this generates the order of the gene segment for the variable region of the heavy chain

Answer 22

Rearrangement of V, D, and J gene segments is guided by flanking DNA sequences called RSS sequences it has a very specific mechanism to ensure that one V will bind to one J which will bind to one D this is created by the process shown which has directionality of our gene segments we have caps on the end of our segments called base pair spacers, which either have 23 base pairs in the middle or 12 - called RSS this is to ensure that the correct segments binds together this is because a 23 spacer can only bind to a 12 spacer → 23-12 space rule so the joining of different segments is not completely random and has some directionality

Answer 23

PROCESS IN L2 S27 TO 32

Answer 24

The T-cell receptor gene segments are arranged in a similar pattern to immunoglobulin gene segments and are rearranged by the same enzymes instead we have an alpha chain and a beta chain which are also located on different chromosomes and have variable regions joining regions and and constant regions the similarity is that the Beta chain is similar to the heavy chain since it has diversity segments as well so the alpha chain will also have 1 recombination events like the light chain and the Beta chain will have have 2 recombination events like the heavy chain

Answer 25

T-cell receptors concentrate diversity in the third hypervariable region which contacts peptide the third complementarity determining hypervariable region of both the alpha and beta chain that really has to recognise the peptides (which is what will differ between diff pathogens) and so the hypervariable region 3 tends to have more diversity than region 1 and 2 of both a and B chains

lecture 1-2 Flashcards

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