Antigen Recognition by T cells and MHC Flashcards
What is SCID?
Severe combined immunodeficiency syndrome- absence of, or few, functional T cells (humoral immunity also lost)
What is Omenn Syndrome?
MIssense mutations in RAG-1 and RAG-2 resulting in partial activity- causes SCID
What must happen before the TCR can leave the endoplasmic reticulum?
Association with 4 proteins– the CD3 complex- and the zeta chain
What portion of the TCR mediates intracellular signaling?
Associated zeta chain
What is the #1 marker for T cells?
CD3
What are the 2 mutually exclusive classes of alpha-beta T cells?
CD4+ and CD8+
What types of T cells are cytotoxic and kills infected cells?
CD8+
What type of MHC presents intracellular pathogens? To what kind of T cells?
Class I; CD8+
What type of MHC presents extracellular pathogens? To what kind to T cells?
Class II; CD4+
What cells express MHC I ? MHC II?
Almost all cells express Class I; Class II only on macrophages, dendritic cells, and B cells
What is antigen processing and presentation?
Antigen processing is the proess by which antigens are cleaved into short peptides that the T cells can recognize; Antigen presentation is the binding of Ag to MHC and movement to the surface
What is the structure of the MHC class I? What subunits form the peptide binding site?
Transmembrane alpha chain complexed with beta2 microglobulin; Alpha 1 and alpha 2 form the binding site
What is the structure of the MHC class II? What subunits form the peptide binding site?
2 transmembrane proteins- alpha chain and beta chain- both of which contribute to the binding site
What is meant by MHC having a ‘promiscuous’ binding specificity?
Their peptide binding sites can bind peptides of many different
Which MHC class can bind to larger peptide
Class II
How is antigen processed and presented via MHC Class I?
Interferons prompt the proteosome to become an immunoproteosome and degrade intracellular pathogenic protein. The TAP transporter proteins take the peptide into the ER where the peptide is assemble in the groove of MHC I after which is is transported to the surface via the Golgi
How is antigen processed and presented through MHC II?
Extracellular material is taken up by phagocytosis into a phagosome which fuses with a lysosome. The phagolysosome degrades the peptide. MHC II enters into the vesicles and are loaded with peptide and transported to the surface
True or False: If no pathogenic peptide is available the MHC is loaded onto the surface empty
False: antigen must be loaded to get to the surface
What is a superantigen? What kind of molecule are most?
An intact protein that is recognized by the T cells without being processed into peptide; Most are bacterial toxins
Why are superantigens so dangerous?
It can activate a large number of CD4+ cells to generate a cytokine storm
To what part of the TCR does a superantigen bind?
They bind to specific V beta families
What are MHC molecules in humans often called?
HLA- Human Leukocyte Antigen complex
How is MHC diversity achieved?
1) Gene families- each individual expresses several genes encoding both classes of MHC 2) Genetic polymorphisms within the genes
What are the protein products of different genes in an MHC class I or II family called?
Isotypes
What are the major MHC class I isotypes?
HLA-A, HLA-B, and HLA-C
What are the major MHC Class II isotypes?
HLA- DP, DQ, and DR
What is a haplotype?
The combination of MHC alleles that is inherited from each parent
In any mating, how many possible combinations of haplotypes are there?
4
Where is most of the polymorphic diversity between MHC allotypes?
Concentration in the sites on the MHC that bind peptide and TCR
What are anchor residues?
Amino acids that are conserved throughout all peptides that bind to a particular MHC
What is MHC restriction?
The principle of T cell biology that dictates that antigen specific T cell responses are restricted by MHC type
True or False: A T cell that responds to a peptide presented by one MHC allotype will not respond to another peptide bound by the same MHC allotype or to the same peptide bound to another MHC allotype
True
True or False: Though the fetus is generally protected from maternal immune reponses, mom still makes alloantibodies to paternal MHC.
True
What is the dominant geentic factor affecting suscetibility to autoimmune disease?
HLA
