chapter 7 Flashcards
Glycoproteins expressed on all nucleated cells: interact with Tc (CD8+ T ) cells
Class I MHC genes
Glycoproteins expressed APC cells: interact with TH (CD4+ T) cells.
Class II MHC genes
Secreted protein: complement and tumor necrosis factor (TNF)
Class III MHC genes
-Member of the Ig superfamily
-Larger 45 kDa glycoprotein α chain
-Smaller 12 kDa β2-microglobulin protein
-peptide binding groove between α1 and α2 domains
Class I molecules
-Member of the Ig superfamily
-Heterodimeric: 33 kDa α chain & 28 kDa β chain
-Both chains pass through the plasma membrane
-A peptide-binding cleft is formed by the pairing of the
α1 and β1 domains
class 2 molecules
occurs when two or more clearly different phenotypes
exist in the same population of a species
Polymorphism
Where do class I and class II molecules exhibit polymorphism?
in the peptide-binding region
How many class I and class II molecules can be expressed per person?
up to 6 class I and 12 class II
How does the limited group of molecules (class I & 2) present the vast diverse array of possible antigen peptide fragments?
A given MHC molecule can bind numerous different peptides, and some peptides can bind to several different MHC molecules
Describe the Class I MHC-peptide interactions:
-present peptides to CD8+ T cells
-some amino acids anchor the peptide into the groove
-other amino acids are available to interact with a TCR
Describe the Class II MHC-peptide interactions:
-present antigen peptides to CD4+ T cells
-some amino acids anchor the peptide into the groove
-other amino acids are available to interact with a TCR
What is the difference between class I and II regarding the nature of the peptide-binding groove?
MHC I is closed at both ends
MHC II is open at both ends
What is the size difference between class I and class II molecules?
class I is 8-10 amino acids
class II is 13-18 amino acids
describe the peptide motifs involved in binding to the MHC molecule for class I:
-anchor residues at both ends of peptide
-generally hydrophobic carboxyl-terminal anchor
describe the peptide motifs involved in binding to the MHC molecule for class II:
conserved residues distributed along the length of the peptide
describe the nature of bound peptide for class I:
extended structure in which both ends interact with MHC groove but middle arches up away from MHC molecule
describe the nature of bound peptide for class II:
extended structure that is held at a constant elevation above the floor of the MHC groove
describe the gene sequence of class I:
-5’ leader exon for signal peptide followed by 5–6 exons
encoding α chain
–Signal peptide is eventually removed
one of a number of alternative forms of the same gene or
same genetic locus (a group of genes)
allele
what is a haplotype?
each set of allele
what is the definition of inbreeding?
-reproduction from the mating of parents who are closely
related genetically
______________________ of mice has allowed for more standardized MHC genotypes to control variability
Inbreeding
Why are MHC alleles codominantly expressed?
-this gives the best chance for an organism to have some capability of presenting all the possible antigen peptides it encounters
Why does codominant expression of MHC alleles make transplantation somewhat dificult?
humans are heterozygous at each locus
How does diversity of class I/II molecules at individual and species levels provide flexibility?
This diversity provides flexibility in responding to
unexpected environmental changes, now and in the
future
Describe the antigen peptides presented by MHC class I:
-intracellular
-includes self peptides
-provides a way for checking that cells are self and are generally healthy
-Can also be used to show which cells have been infected with
viruses or are abnormal
Describe the antigen peptides presented by MHC class II:
-extracellular
-more restricted
-generally found on APC
MHC class II is primarily restricted to _________________.
antigen-presenting cells (APC)
How can MHC expression change with genetic regulatory components?
promoters that drive up transcription during times of infection
How can MHC expression change with viral interference?
viruses like to shut down MHC Class I expression
How can MHC expression change with cytokine-mediated signaling?
some cytokines expressed during infection/disease can drive up/down MHC expression
How do class II MHC alleles play a critical role in immune responsiveness?
Different capability to present antigens may dictate overall strength of response from individual to individual
T cells are restricted to recognizing peptides
presented in the context of ____________________.
self MHC alleles
the property of recognizing antigenic (foreign)
peptides only in the context of self MHC molecules
Self-MHC restriction
Only _____________antigen peptide fragments can be recognized by T cells.
processed
What type of processing is required for Class I presentation?
cytosolic or endogenous processing
What type of processing is required for Class II presentation?
exogenous processing
Describe the endogenous pathway of antigen processing and presentation:
-peptides are generated by proteasomes then tagged by Ubiquitin for degradation by proteasomes
-peptides are transported from the cytosol to the RER by TAP molecules
What are TAP molecules?
Transporter associated with antigen processing in the RER membrane that move fragments
cleaves ubiquitinated proteins into fragments that pair better with MHC molecules
immunoproteasome
How do chaperones aid peptide/MHC class I assembly?
-Calnexin, calreticulin, and tapasin help fold MHC class I and put it in close proximity to TAP
-ER aminopeptidase ERAP1 trims long peptides to a suitable
size for MHC class I grooves
Describe the exogenous pathway of antigen processing and presentation:
-peptides are generated from internalized antigens in endocytic vesicles
-particles are taken in with endosomes
-simultaneously, MHC class II molecules are produced and exported from the ER in vesicles
How does the invariant chain guide transport of class II MHC molecules to endocytic vesicles?
– Invariant chain (Ii, CD74) prevents peptides from
binding to the groove too early in the ER
– Ii also uses sorting signals in its cytoplasmic tail to
direct MHC class II molecule
What is the primary cross-presenting cell type?
dendritic cells
Describe cross-presentation of exogenous antigens:
– Exogenous antigens are redirected to the endogenous presentation pathway
– This allows for their presentation on MHC class I molecules,
priming CD8+ T-cell responses
– Dendritic cells are the only APCs (so far) to exhibit this activity
in vivo
What is the mechanism and function of cross-presentation?
-To prevent redirection of self-antigens into APC pathways, dendritic cells may need “license”
-If DC can present foreign antigen to
CD4+ helper T cell, it gets “license” to redirect exogenous Ag into the endogenous pathway
-“License” might be back/forth cytokine signal between the APC and helper T cell, a situation right for cross-presentation
How are nonprotein antigens recognized by T cells?
they load on the CD1 family
what is the definition of homozygous?
having the same alleles at a particular gene locus on homologous chromosomes
what is the definition of heterozygous?
having different alleles at one or more corresponding
chromosomal loci
