Linking Innate and Adaptive Immunity 3 Flashcards
what do TCRs recognize? where?
peptide-MHC complexes on the surface of APCs
what is an immunological synapse?
T cell:APC contact, with the TCR complex
what are the 4 components of the TCR complex? describe each component’s location in the complex
- TCR –> in the middle
- CD3 –> 1 on either side of TCR
- zeta chain –> 2 inside cell
- ITAM –> on intracellular part of CD3 and zeta chains
what is ITAM?
Immunoreceptor Tyrosine-based Activation Motif
what does the TCR complex trigger?
intracellular signaling
what type of molecule is TCR?
HETERODIMER
what type of proteins are involved in TCR?
transmembrane proteins
is TCR secreted?
no, it is membrane-bound
what are the 2 main types of TCR? which is most common?
- alpha-beta TCR (most common)
- gamma-delta TCR (<10%)
what are the 2 types of chains on the most common TCR?
- ALPHA
- BETA
what does clonotypic mean?
the cells of a given clone all have identical receptors
what are the 2 main subunits of each chain?
- Variable (V)
- Constant (C)
how many TCR and BCR are possible? why?
billions! to allow for increased specificity
how does the number of adaptive immune receptors compare to the number of innate immune receptors? why?
there are <100 innate immune receptors (PRRs) because they don’t need to be very specific
BCR and TCR genes undergo __________
BCR and TCR genes undergo DNA rearrangement
what are the 4 gene segments of BCR and TCRs?
- Variable (V)
- Diversity (D)
- Joining (J)
- Constant (C)
what are gene segments?
short DNA sequences
what domains are in the alpha chain?
V, J, C
what domains are in the beta chain?
V, D, J, C
where does TCR rearrangement occur?
in the thymus
what is another term for gene rearrangement?
somatic recombination
what is somatic recombination/gene rearrangement?
recombination of gene segments in TCR genetic loci to make a functional gene
describe gene rearrangement for alpha chain
1 V, J, and C are selected in the DNA to be transcribed and translated into an alpha chain
describe gene rearrangement for beta chain
1 V, D, J, and C are selected in the DNA to be transcribed and translated into a beta chain
how many variations of TCRs are possible? how is this variability achieved?
billions of variations possible
many combos of each subunit are possible, and many combos of alpha and beta chains are possible
why don’t TCRs recognize the peptide by itself?
TCRs only recognize the peptide when MHC is present –> TCR interacts with both peptide and MHC
what are the 2 types of APCs?
- Professional APC
- Non-professional APC
what 3 types of cells are professional APC?
- DCs
- macrophages
- activated B cells
what type of cells are non-professional APC?
all nucleated cells in the body
what type of MHCs do professional APC express?
- MHC Class I
- MHC Class II
what do professional APCs express when activated?
express costimulatory molecules when activated
what type of MHCs do non-professional APC express?
MHC Class I only
when do non-professional APC express MHC Class I?
under normal conditions to show that they are healthy
do non-professional APC express costimulatory molecules?
no
what do MHC Class I molecules bind and present?
bind and present peptides generated within the cell –> endogenous proteins, self proteins
what do MHC Class II molecules bind and present?
bind and present peptides of extracellular origin –> exogenous peptides
what type of cells do MHC Class I molecules activate?
CD8+ T cells
what do CD8+ T cells become when they become effector cells?
cytotoxic T cells
what type of cells do MHC Class II molecules activate?
CD4+ T cells
what do CD4+ T cells become when they become effector cells?
T helper cells
what subunits are in the MHC Class I molecule?
- 1 transmembrane alpha protein
- 1 beta-microglobulin protein
- 2 alpha proteins that make up the peptide-binding cleft
what subunits are in the MHC Class II molecule?
- 1 beta, 1 alpha transmembrane proteins
- 1 beta, 1 alpha proteins that make up the peptide-binding cleft
what subunit of MHC Class I molecule is present in every MHC Class I molecule?
beta-microglobulin
what are the 3 components of the MHC Class I molecule that is required to be stably expressed on the cell surface?
- peptide
- MHC Class I alpha chain (for 3 subunits)
- beta-microglobulin
what are the 3 components of the MHC Class II molecule that is required to be stably expressed on the cell surface?
- peptide
- MHC Class II alpha chains
- MHC Class II beta chains
each chain of the MHC has several _____________ domains
each chain of the MHC has several IMMUNOGLOBULIN-LIKE domains
what are immunoglobulin-like domains?
secondary structure in many immune molecules
besides TCRs, where are immunoglobulin-like domains found?
adhesion molecules
what are the 4 components of immunoglobulin-like domains?
- ~100 amino acids
- alpha helices
- beta sheets
- stabilized by disulfide bond
where is the more conserved location of MHC located?
closer to cell membrane
where are the most variable regions of MHC located?
mostly around peptide-binding cleft
what is the shape of MHC?
MOOSE
how is beta-microglobulin bound to the rest of MHC?
bound at transmembrane alpha domain by non-covalent bond
what length of peptides do MHC Class I molecules bind?
short peptides –> 8-10 amino acids
what length of peptides do MHC Class II molecules bind?
length doesn’t matter
what allows for a stable interaction between TCR and peptide-MHC?
co-receptors
why are co-receptors required?
because TCR and peptide-MHC is a low affinity interaction
which co-receptor is used for MHC Class I ?
CD8
which co-receptor is used for MHC Class II?
CD4
co-receptors physically interact with __________
co-receptors physically interact with MHC
describe the structure of CD4
- single chain transmembrane protein
- 4 Ig-like domains (all identical)
describe the structure of CD8
- heterodimer linked by disulfide bond
- each transmembrane chain has 1 Ig-like domain
what are the 2 roles of CD4 and CD8 co-receptors?
- bind MHC molecule and enhance affinity of TCR-pMHC interaction
- initiation of intracellular signaling from TCR (signal 1)