T cell immunity I Flashcards
what is behind the immunological rejection skin grafts/other organs?
T cells
which were discovered when the surgical removal of the thymus in the recipient was found to prevent immunological rejection of skin grafts/other organs
describe the structure of the T cell receptor
comprised of a pair of cell surface proteins
——- alpha chain and a beta chain which are linked together via disulfide bonds
the variable region of the alpha and beta chain make up the antigen binding site
the variable region varies among T receptors of different cells
the constant region stays the same among T cell receptors of individual cells
very short cytoplasmic tail - receptor must rely on the support of other proteins to transmit signals as it’s not capable to do so by itself
how does the TCR recognize an antigen?
the epitopes recognized by TCRs are often buried, thus, the antigen must first be broken down peptide fragments to make the epitope more easily accessible for the MHC
the epitope peptide binds to a self molecule, an MHC molecule
TCR binds to a complex of MHC molecule and epitope peptide
TCR can only recognize the peptide if presented with the MHC
where do the peptides that interact with MHC molecules come from?
inside the cell
—- self proteins: from the genetic code
—- viral infections: viruses are obligate intracellular parasites, making proteins inside the cell
outside the cell
—- bacterial infections
—- parasitic infections
—- self proteins: when a self protein is “eaten” by phagocytic cell – when a cell bursts open, releasing proteins
what are the types of MHC molecules, describe the structure, and what T cells they interact with?
MHC II
- made up of 2 proteins: alpha and beta chain
- interacts with CD4 T cells that eventually become helper T cells
- CD4 is the protein on the T cell that stabilizes the interaction
MHC I
- made up of 2 proteins: alpha chain and a small beta-2-microglobulin
interacts with CD8 T cells that will eventually become helper T cells
- CD8 is the protein on the T cell that stabilizes the interaction
what is MHC restriction?
the fact that TCRs can only recognize antigens displayed as peptide fragments bound to MHC molecules
in regards to MHC molecules, what’s the basis of immunological rejection between individuals (transplants)? and why is this the case?
the basis of immunological rejection between individuals is due to the large diversity of MHC molecules in people, often leading to mismatched transplants
evolutionary survival advantage against infectious disease
MHC is the most allelic-ly diverse proteins known in the human genome; for each protein, there’re thousands of alleles/allotypes in people
difference in alleles is what helps prevent pandemics from wiping out human populations
which part of the MHC molecule varies per person?
diversity in MHC is found in the binding groove, the area which binds to the peptide
makes sense because we have different ranges of what peptides our MHC recognizes! and recognition occurs at the binding groove
what type of cells express MHC class II/I molecules?
MHC class II is expressed by antigen presenting cells (B cells, macrophages, dendritic cells) and thymic epithelial cells
MHC class I is expressed by all nucleated cells (exclusion: RBCs)
what’s the importance of thymic epithelial cells?
thymic epithelial cells play a role in “educating” T cells during development, specifically clonal selection
describe the binding groove of MHC class II. domains? stabilization with peptide? type of binding groove? length of peptides that bind to it?
alpha 1 and beta 1 domain makes up the peptide binding groove (binding groove is between 2 proteins)
domains it has: alpha 1 & 2 and beta 1 & 2
peptide binding is stabilized by amino acid contact between alpha helices (the wall) and beta sheets (the floor)
has an “open” peptide binding groove that binds peptides of 13-24 amino acids
describe the binding groove of MHC class I. domains? stabilization with peptide? type of binding groove? length of peptides that bind to it?
alpha 1 and alpha 2 domain make up the binding groove (comes from 1 protein)
domains it has: alpha 1, 2, & 3 and beta 1
interactions of peptide stabilized by how hydrophobic/hydrophilic the interactions of the peptides with individual amino acids
has a “closed” peptide binding groove that binds peptides of 8-10 amino acids
are there restrictions to the peptides the MHC molecules can bind?
in regards to length!
MHC class II binds to peptides of 13-24 amino acids
- can also bind to peptides of shorter length - no hard requirement
MHC class I binds to peptides of 8-10 amino acids
describe the process of assembly for MHC class I molecules and their peptides
THINK PROTEASOME-MEDIATED DEGRADATION!
proteasome chews up the proteins and spits it out into fragments that are 8-10 amino acids long
fragments are transported to the endoplasmic reticulum via TAP, a protein transporter
in the ER, the fragments are folded by chaperone fragments
peptides spontaneously bind to the peptide binding groove of the MHC via hydrophilic/hydrophobic interactions
the MHC class I and peptide complex is transported thru the golgi to the cell surface
where it will be recognized by CD8+ T cells (cytotoxic T cells)
describe the process of assembly for MHC class II molecules and their peptides
THINK PHAGOCYTOSIS!
materials brought into the cell via phagocytosis in phagosomes/lysosomes
which are then acidified – (acid) activated enzymes cut up the proteins into small randomly sized peptide fragments
——- MHC class II uses an “open” conformation, therefore, they can bind long and short fragments
lysosomes with chopped up material will merge with a compartment containing MHC II
MHC II and peptide complex exported to the cell surface
