14 – Linking innate & adaptive: Exceptions & MHC genetics Flashcards
3 Exceptions
Cross-presentation
Presentation of cytosolic peptides by MHC class II molecules
-Peptides in cytosol
Allorecognition
Cross presentation by …
DC can cross-present antigens
Exogenous antigens are redirected to endogenous presentation pathway
DC are the only APCs to be able to do this
Cross presentation by DCs example:
Viruses phagocytosed by DC = exogenous antigens
Virally-infected cells phagocytosed & viral peptides are presented on MHC I molecules
Mechanisms & functions of cross presentation
DC need license – permission to redirect
DC can present foreign antigen to CD4+ helper T cell (exogenous pathway) & get licensed to redirect exogenous Ag into endogenous pathway from T cell
License = cytokine & ligand signal between APC/helper T cell
-Allow presentation on MHC class I molecules
-Priming CD8+ T cell responses
Need to have activated CD4+ T cell first to then license and then cross-present
Presentation of cytosolic peptides by MHC class II molecules occur via ..
autophagy:
Digestion & breakdown by a cell of its own organelles & proteins in lysosomes
Autophagosome
Specialized vesicles that contain cytoplasmic content & fuses with lysosomes
mechanism of Presentation of cytosolic peptides by MHC class II molecules
1.Parts of cytoplasm taken in autophagosomes
2.Proteins degraded
3.Links up to exogenous pathway –> MHC II
Presentation of cytosolic peptides by MHC class II molecules example:
Some pathogens adapted to resist intracellular killing & macrophages in which they live require stimulation by cytokines to kill pathogens
TCR : … restriction
MHC restriction
Cell responses are MHC restricted
MHC restriction = given T cell can recognize specific peptides only when bound to a specific self MHC molecule
TCR restriction Example
strain A animals only respond to Ag presented by strain A APCs but not by strain B APCs
TCR specific to
Peptides
MHC
Allorecognition
recognition of non-self MHC by some T cells in body
1-10% of all T cells in an organism, can react to non-self (allogenic) MHC molecules (allo-MHC)
allorecognition: main mechanism of…
rejection of transplanted organs between genetically different individuals of same species
Direct allorecognition
recipient T cell recognition of donor/transplant MHC molecules expressed on surface of donor cells
Self T-cells recognize donor MHC is non self –> proliferate & differentiate –> try to get rid of them
Indirect allorecognition
recognition of processed donor peptides presented onto recipients’ own APCs via self MHC
Self-APC can take up pieces of donor APC –> process –> Resent to T cell
Gene
segment of chromosome that controls specific characteristics
Encodes for protein
Allele
one specific form of a gene
Locus
specific chromosomal location of gene
MHC molecules coded by … genes
on which chromosome?
HLA genes – human leukocyte antigen
Found in cluster of genes on chromosome 6 in humans
MHC genes – divided in .. classes, what are they?
2 main class - POLYGENY
MHC Class I genes – code for α chain
HLA-A
HLA-B
HLA-C
MHC Class II genes – code for α & β chain
HLA-DR
HLA-DQ
HLA-DP
HLA-DM
HLA-DOA
HLA-DOB
Polymorphism
Multiple variations (forms)/alleles - exists for each gene
Multiple allelic variants of each of MHC Class I & II genes in population
HLA-A is example of
gene
HLA-A1 to HLA-A2041 is example of
allele
polymorphism: allele
2 or more alternative forms of a gene at a particular locus
Haplotype
particular combination of MHC alleles found on a single chromosome
Everyone inherits 1 haplotype from each parent
MHC allele … expressed
makes … difficult
codominant
Both maternal & paternal MHC genes are expressed
Best chance of presenting all possible antigen peptide it encounters
Makes transplantation difficult: Humans are heterozygous at each locus
Polygeny
Each individual has many copies of related genes
multiple gene with same function – but slightly different structures
Inherit 3 different MHC-I alleles from each parent = 6 alleles can be expressed in one person
-HLA-A, HLA-B, HLA-C allele per chromosome
polygeny result in…
Results in high degree of variance in MHC expression in population
Differences clustered at aa location within …
groove sites
Differences clustered at aa location
Helps facilitate
presentation of different variety of peptides
Different peptides binding specificities
If areas outside the binding groove were altered too much
can affect structure conformation & folding of MHC molecule
MHC molecules can bind many different peptides =
Some peptides can bind to different MHC molecules
