Lecture 10: MHC Genetics, Structure and Peptide Selection Flashcards

1
Q

What makes it difficult for MHC to detect pathogenic peptide ligands?

A

the number of potential MHC peptide ligands that can be generated by degradation of self and non-self proteins is vast

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2
Q

How is MHC able to detect pathogenic peptide ligands?

A

these molecules are able to bind a large number of different peptides, in the hope that some of those peptides will belong to the pathogen

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3
Q

How are MHC molecules able to bind many different peptides?

A

each MHC molecule has a single binding groove which can bind to many different peptide fragments of different lengths of amino acids

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4
Q

What are the two “faces” of antigenic peptides?

A

one is exposed to the TCR and the other is buried in the MHC binding groove

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5
Q

What are anchor residues?

A

“pockets” in the peptide binding site of MHC molecules that can only accommodate certain residues, but the interaction between the pocket and those residues is very strong

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6
Q

What is the role of the residues pointing outside of the MHC (variable residues)?

A

since they contribute little to binding, these residues can vary without compromising the strength of the MHC-peptide interaction

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7
Q

How many different peptides can the binding groove of an MHC molecule accommodate?

A

thousands of different peptides sharing the same “anchor” residues

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8
Q

An MHC molecule can present a ___ number of different peptides, but these still represent a ___ fraction of the whole ___.

A

large
small
peptidome

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9
Q

How is MHC able to expand the number of different peptides that cells are able to present?

A

MHC genes are polymorphic i.e. polymorphism varies the structure of the peptide binding site and each allele binds a different set of proteins

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10
Q

What are the implications of polymorphism?

A

we are diploid and we can express different MHC allelic variants in each locus -> this means that since there are three loci encoding MHC I and three loci encoding MHC II, each individual can have up to six genes encoding for MHC I and six encoding for MHC II

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11
Q

What does it mean if each individual can have up to six genes encoding for MHC I and six encoding for MHC II?

A

each individual can express up to six different MHC class I molecules and six different MHC class II molecules

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12
Q

What is the nature of the genes that encode MHC molecules?

A

they are clustered

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13
Q

What are HLA and H-2 complexes?

A

individual names for MHCs in humans and mice respectively

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14
Q

How many allelic variants are there in each locus?

A

varies but it is very large

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15
Q

What does polygeny and polymorphism allow?

A

allows each MHC molecule to present a larger fraction of the peptidome

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16
Q

How are MHC molecules able to present the entire self and pathogen “peptidome”?

A

each individual can present a different (but overlapping) set of peptides -> one MHC molecule may not be able to present a pathogen, however a different MHC molecule will be able to

17
Q

What does the TCR interact with?

A

residues from both the antigenic peptide and the MHC molecule

18
Q

How many TCRs can recognise the MHC-peptide complexes that can be potentially presented by an individual’s MHC?

A

only a fraction

19
Q

Which T cells are selected in the thymus and go into circulation?

A

only those that can recognise your MHC

20
Q

What do all the selected T cells express?

A

TCRs which can interact ”a bit” with the peptide-binding site of at least one of your MHC molecules, but not so strongly enough to cause “recognition”

21
Q

What do normal T cells “ignore”?

A

the self-peptides but some of them will interact with both the MHC and the peptide strongly enough to “recognise” the complex if the peptide is foreign (new)

22
Q

What do T cells of each individual recognise?

A

only the antigenic determinants presented by the MHC allotypes of that individual