lect 5 - antigens processing

antigens are

any substance that binds specifically to an antigen receptor

types of antigen receptor

antibody, b cell receptor, t cell receptor

antigens are made up of

proteins, carbs, other polymers (depends on whether BCR or TCR)

TCRs do not bind

intact soluble antigens

TCRs recognize a

composite ligand consisting of peptide and MHC

all antigens are recognized by specific

lymphocyte receptors or by antibodies, but only some antigens are capable of activating lymphocytes

immunogens are

an antigen that can induce an immune response (B/T cell)

haptens are

antigens that cannot induce an immune response alone, but when attached to a more complex molecule (carrier) is immunogenic

hapten-carrier complex is

immunogenic

penicillin can act as a

hapten, binding host proteins and inducing drug allergy

conjugate vaccines link a weakly immunogenic carb to a protein carrier to generate

a stronger, longer-lasting immune response

factors that make a good immunogen

complex, organic, degradable, large, foreignness in context

size, complexity, and foreignness influence

immunogenicity

epitopes are the

recognized parts of an antigen

antibodies are

secreted BCRs

2 other names for epitopes

determinant, antigenic determinant

different antigen receptors can recognize

the same antigen but different epitopes

b cells and t cells have distinct requirements for

antigen recognition

BCR/antibodies recognizes

intact antigen

TCR recognizes

processed antigens

BCR/antibody is made up of

proteins, carbs, lipids, other structures

BCR/antibody epitope shape

linear, conformational

BCR/antibody, is processing required?

no

TCR is made up of

usually peptides

TCR epitope shape is

linear sequence bound to MHC

TCR, is processing required?

yes

neoantigens are

an important concept in antiviral and anticancer

some viral proteins undergo

proteolytic cleavage or conformational changes that create/reveal new epitopes

in cancer, transformed cancerous cells can express

neo antigens, ectopically expressed antigens or mutated antigens

personalized cancer vaccines and t cell therapies target

tumor neoantigens while largely sparing normal tissues

one protein can contain many

potential b cell and t cell epitopes

the antigen will have to be

processed into peptides to be presented to a t cell to be a t cell epitope

TCR contacts both the

antigenic peptide and the MHC molecule

linear epitopes are made of

continuous residues

conformational epitopes are made of

discontinuous residues brought tg by protein folding

types of MHC molecules

MHC class 1, MHC class 2

MHC class 1 is expressed on

all nucleated cells

MHC class 1 presents

peptide to CD8+ t cells

MHC class 1 presents what source of antigen

intracellular antigens

MHC class 1 binds to how many peptide lengths

8-11 amino acid peptides

MHC class 2 is expressed only on

professional antigen presenting cells

MHC class 2 presents

peptides to CD4+ t cells

MHC class 2 presents what source of antigen

extracellular antigens

MHC class 2 binds to what protein length

12-23 amino acid peptides

MHC genes are

germline, inherited (no genetic rearrangement like antigen-receptors)

MHC molecules are

polygenic, several MHC genes in one individual

MHC genes are co-dominant meaning

maternal and paternal alleles are expressed

MHC is the most

highly polymorphic region in the genome, there are many alleles in the population

HLA

human leukocyte antigen

DLA

dog leukocyte antigen

ELA

equine leukocyte antigen

MHC class 3 genes do not

encode MHC molecules

MHC haplotype is

a set of alleles inherited from one parent form an individual’s haplotype

allele is

one of several alternative forms of the same gene on a chrmooome

recombination is the

crossing over in chromosomes

recombination rarely

occurs in MHC haplotype

polymorphisms accumulate

over time

it is unusual for unrelated individuals to have

identical haplotypes

HLA typing is important for

transplant immunology

MHC proteins bind

peptides and present them to TCRs to activate specific T cells

the structure of the MHC binding pocket determines

which peptides can bind

each MHC allele has a

peptide-binding groove w/a characteristic binding preference

haplotype determines the

repertoire of peptide antigens presented

note that TCR contacts both

peptide and MHC

TCR recognizes a

particular peptide only when an appropriate self-MHC molecule presents it

cytosolic proteins feed

MHC 1 pathway

endocytosed proteins feed

MHC 2 pathway

MHC class 1 presentation partner

CD8+ t cells (cytotoxic t cells, CTLs, Tc cells)

MHC class 2 presentation partner

CD4+ t cells (helper T cells, Th cells)

proteasome in the cell cytoplasm serve as

a garbage disposal

cytosolic proteins are

degraded into peptides

proteasomes includes

misfolded, mutant, damaged, excess, or targeted proteins

peptides are transported by

TAP (transporter associated w/antigen processing)

peptides are transported from

cytoplasm to the ER where they are loaded onto new MHC 1 proteins

class 1 is transported to the

cell surface to present peptides to CD8 T cells

MHC 1 can present peptides from

self or non-self cytosolic proteins, the proteasome, MHC, and TAP do not discriminate

steps of class 1 antigen processing and presentation

cytosolic protein degradation by the proteasome, peptide transport into ER by TAP, peptide loading onto MHC 1, surface presentation to CD8 T cells

proteasome, TAP, MHC do not discriminate and can present

peptides from self or non-self cytosolic proteins

who presents peptides on MHC class 1?

nearly all nucleated cells

nearly all nucleated cells present on MHC 1 because they

provide a survey of everything going on w/in a cell, viral infection, tumor antigen

presenting peptides to CD8 t cells for

potential recognition and killing

step 1 of class 2 antigen processing/presentation

extracellular proteins are endocytosed, the endosomes fuse w/lysosomes and degrade the proteins within

step 2 of of class 2 antigen processing/presentation

class 2 proteins are folded in the ER, but do not load peptide

step 3 of class 2 antigen processing/presentation

invariant chain blocks the binding groove and targets class 2 to endosomal/lysosomal compartments

step 4 of class 2 antigen processing/presentation

invariant chain is degraded in the endosome, peptides produced in the endosome are loaded onto class 2

step 5 of class 2 antigen processing/presentation

class 2 is transported to the cell surface where it presents peptide antigens to CD4 T cells

binding of invariant chain to MHC 2 prevents it

from behaving like class 1 MHC

professional APCs are

dendritic cells, macrophages, B cells

all professional APCs can

endocytose, responding to insult or thru specific recognition

professional APCs present peptides from the

extracellular milieu to CD4 t cells to help coordinate the appropriate response

presenting on MHC 2 directly benefits the APC b/c

CD4 t cells activate and signal back to the b cell or macrophage

MHC 2 expression on macrophages

low levels, induced by PAMPs, DAMPs, cytokines, upregulated on activation

MHC 2 expression on dendritic cells

always expressed, upregulated on activation

MHC 2 expression on B cells

always expressed, upregulated on activation

macrophages present what antigens and on which MHC

extracellular antigens via MHC 2

dendritic cells present what antigens and on which MHC

intracellular and extracellular antigens via MHC 1 and MHC 2

b cells present what antigens and on which MHC

extracellular antigen that binds their antigen-specific Ig receptor via MHC 2

macrophages are found in

lymphoid tissue, CT, body cavities

dendritic cells are found in

lymphoid tissue, CT, epithelium, peripheral tissues

b cells are found in

lymphoid tissue and blood