tompkins- antigens, antigen processing, and presentation

define antigen

any substance that binds specifically to an antigen receptor

T/F: all antigens are recognized by specific lymphocyte receptors or antibodies but only some antigens are capable of activating lymphocytes

true

examples of antigens

antibody, BCR, TCR

define immunogen

an antigen that can induce an immune response (activates b or t cells)

what are the factors of a good immunogen?

complex, organic, degradable, large, foreigness in context

examples of immunogens (weakest to strongest)

amino acids, haptens, lipids, steroids, carbohydrates, proteins

define hapten

an antigen that is not immunogenic by itself, must be attatched to a more complex molecule (carrier)

real life applications of haptens

penicillin is a hapten that can bind with a host protein, conjugate vaccines link to carriere to generated a longer and stronger immune response

define epitope

the part of the antigen that is recognized, also called the determinant or antigenic determinant

can different antigen receptors recognize the same antigen if they have different epitopes?

yes

compare the antigens BCR and TCR recognize

BCR- intact antigen, TCR- processed antigen

what chemical forms to BCR and TCRs recognize?

BCR- proteins, carbohydrates, lipids, other structures and TCR- usually peptines

what epitopes do BCR and TCR recognize?

BCR- linear or conformational, TCR- linear sequence bound to MHC

which receptors require antigen processing in order to recognize?

TCRs

which receptor is interchangable with antibody?

BCR

2 possible Ab/BCR epitopes

continuous/linear and discontinuous/conformational

TCR epitopes

CD4 and CD8

what molecules are responsible for presenting peptides to the T cell?

MHC I or MHC II

which b cell epitope is sensitive to denaturization?

conformational determinant/epitope

describe a linear determinant/epitope

a straight, ubroken chain of amino acid residues instead of a 3D folded shape— NOT sensitive to degradation (does not rely on protein folding and will remain intact after denaturization)

define neoantigens

when some viral proteins undergo proteolytic cleavage or conformational changes that create/reveal new epitopes (mutated antigens)

what is the clinical relevance of neoantigens?

canger cells often express neoantigens— t-cell therapies can target tumor neoantigens

how many potential b and t cell epitopes can be contained in one protein

multiple— can be linear or conformational

what does MHC stand for?

major histocompatibility complex

what are the 2 types of MHC molecules?

MHC class I and MHC class II

describe MHC class I

expressed on all nucleated cells, presents peptide to CD8+ T cells, for INTRACELLULAR antigens, binds short (8-11) amino acid peptides

describe MHC class II

expressed only on professional APCs, presents to CD4+ T cells, for EXTRACELLULAR antigens, binds long (12-23) amino acid peptides

‘presentation partner’ of MHC class I

CD8 + t cells

‘presentation partner’ of MHC class II

CD4+ t cells

what does it mean when we say MHC molecules are germline?

genes are inherited and do not undergo antigen-receptor-style gene rearrangement

what does MHC class III encode?

other immune-related proteins, NOT peptide presenting MHC molecules

what does it mean when we say MHC molecules are polygenic?

several MHC genes in one individual

what does it mean when we say MHC genes are co-dominant?

maternal and paternal alleles are expressed

what does polymorphic mean? what is the most highly polymorphic region in the genome?

many alleles in the population; MHC region

describe the MHC of identical twins vs siblings

identical twins have the SAME MHC, siblings have potentially different MHC rearrangements

what is the effect of a restricted MHC locus?

less resistance to diseases

is recombination common in MHC?

no it is rare, typically a stable genome

what is the clinical application of HLA typing?

transplant immunology

MHC class I antigen processing and presentation

proteasome (cytosolic proteins degraded to peptides), peptides transported by TAP to ER, loaded into MHC I to cell surface, presented to CD8 T cells for potential recognition and killing

which MHC class can present peptides from self or non-self cytosolic proteins, proteasome, MHC, and TAP?

MHC class I

MHC class II antigen processing and presentation

extracellular proteins are endocytosed by professional APCs, endosomes fuse with lysozymes and degrade proteins within, class II proteins folded in ER (but do not load peptide), invariant chain blocks binding groove and targets class II, endosome is degraded and peptides produces in the endosome are loaded onto class II, class II transported to cell surface— presents to CD4 T cells

what are three antigen presenting cells?

macrophages, dendritic cells, B cells

do all professional APCs also express MHC class I?

yes, all professional APCs can present peptides using MHC class I

when is macrophage MHC II expression increased?

PAMPs, DAMPs, and cytokines can induce expression; activation increses it

how does MHC II expression in DCs and B cells compare with macrophages?

DCs and B cells always express MHC II, expression increases with activation. macrophages have low basal expression that increases upon activation

what is the main t cell activation role of dendritic cells?

inactivate naive t cells

what do macrophages present and to which t cells?

ingested microbial antigens on MHC II to effector CD4 t cells

how do B cells capture antigen for presentation?

antigen binds to BCR and is taken up and processed, then presented on MHC II

which MHC classes can dendritic cells use to present antigens?

MHC I and MHC II (present both intracellular and extracellular antigens)

specialized role of dentritic cells

activstr naive t cells

specialized role of macrophages

present ingested microbes to effector CD4 t cells

specialized role of b cells

present specifically captures antigens to helper T cells

TCR-MHC-peptide interactions

MHC proteins bind peptides and present them to TCRs to activate specific T cells, structure of MHC binding pocket determines which peptides can bind

what is MHC restriction?

a TCR recognizes a particular peptide ONLY when the appropriate self MHC molecule presents it

which APC can initiate adaptive immune responses? (survey periphery, brings to lymph nodes, presents)

dendritic cells

which APC can cross-present peptides to CD8 T cells?

dendritic cells

immunodominance

out of many possible peptides in an antigen, T cells respond most strongly to ONLY a subset

what effects immunodominance?

MHC specificity, proteases, stability, TCR, etc

alleloreactive t cell activation

activation of t eclls when they recognixe another individuals MHC molecules potentially causing transplant rejection

superantigen t cell activation

nonspecific activation of large number of t cells