Adaptive immunity 3 Flashcards
(25 cards)
describe the structure of a T cell receptor
2 polypeptide chains of the same size
no heavy or light chains
(Alpha chain resembles light, Beta resembles heavy)
variable, constant + transmembrane regions
all variation comes from the 3 variable loops in the 2 chains
always membrane bound
what are CDRs?
complementary-determining regions
part of the variable chains
- where antigens bind
what generates T-cell receptor diversity?
what does this process use?
gene rearrangement
- addition of P + N nucleotides
uses RAG1 + RAG2
what are the loci of a and b chains?
a = chr14 b = chr7
what rearrangement is required for a functional a chain TCR?
what about for a b chain locus?
need a V and J regions to recombine
need a VDJ recombination
where is TCR diversity generated?
in the CDRs
= CDR1-3
how to T cell loci recombine?
T-cell specific TFs open up chromatin at TCR loci
-> allows recombination
TCRs are only expressed when…?
where are these proteins located?
when in a complex with other proteins (CD3 complex)
CD3 gamma, delta + epsilon closely i=linked on chr11
zeta chain encoded on chr1
why is the TCR complex with CD3 necessary?
without CD3 complex,
cytoplasmic tails of TCR are too short to activate signal transduction when an antigen binds
what is the alternative TCR form on some T cells?
gamma:delta receptor
what form must antigens be in for TCRs to recognise them?
what form are these antigens in?
bound to MHC molecules
short peptides
what are the 2 main classes of T cell?
what do they recognise?
CD4
= co-receptor required for T cell recognition of MHC II peptides
CD8
= co-receptor required for T cell recognition of MHC I peptides
what are the functions of CD4 and CD8 positive T cells?
CD8 positive
= cytotoxic T cells
CD4 positive
= T helper cells
- can be divided further:
e.g. TH1 cells activate tissue macrophages to take up antigen
what are the 2 classes of MHC molecules?
MHC I
- present peptides derived from intracellular antigens
MHC II
- present peptides derived from extracellular pathogens
- only on specific APCs e.g. macrophages or DCs
what are MHC molecules?
membrane glycoprotein
bind to an antigen + present it to T-cells
class I and II have similar 3D structure but are formed in different ways
what are the different domains within MHC I and MHC II molecules?
MHC I:
a1, a2, a3 + b2-microglobulin
MHC II:
a1, a2, b1 + b2
how do CD4 and CD8 work?
they form contact with the MHC molecule + strengthen the interaction
they do not bind to the peptide being presented
what limits the length of peptides that can bind to MHC molecules?
how long are MHC I peptides usually?
what determines whether or not a peptide will bind to an MHC I?
the length of the peptide-binding groove
9 amino acids long
the N and C-termini
what length are MHC II peptides?
why are these longer?
13-25 amino acids
they aren’t pinned down in the peptide binding groove at their N and C-termini
describe antigen processing and presentation by MHC I molecules
- protein antigen (e.g. viral) enters cell
- peptides are generates by proteasome in cytosol
- peptides transported into ER lumen by TAP (transporter associated with antigen processing)
- associates with MHC I
- transported to cell surface
what happens if proteins are not fully folded in the ER?
held in the ER by chaperones
e.g. alpha subunit half by calnexin until it associated with beta2-microglobulin
what proteins do MHC1 molecules form a complex with before they can leave the ER?
what does this ensure?
calreticulin
tapasin
TAP
MHC I cannot leave the ER unless they have bound peptide
how are MHC I exported from the ER to the cell surface?
via vesicles through the Golgi Apparatus
describe MHC II presentation process
- antigens then up by phagocytosis or endocytosis
- degraded by proteases in lysosomes
- loading of peptides onto MHCII via MHC class II compartment
- gets transported to cell surface
