11. antigen recognition by T lymphocytes & MHC

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11 Terms

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MHC class I binding cleft is formed by _______

α1 and α2 domains (α chain only)

2
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MHC class II binding cleft is formed by ______

α1 and β2 domains (α and β chains)

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CD8 molecules bind ____

α3 domain of the MHC class I molecule

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CD4 molecules bind ____

β2 domain of MHC class II molecule

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sequence motif

set of amino acids that allows peptide to bind to MHC binding cleft

  • often 2nd-3rd a.a. (amino terminal end); 9th a.a. (carboxy terminal end)

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anchor residue

amino acids that make up sequence motifs

  • side groups of a.a. insert into pockets in floor of peptide binding cleft and anchors peptides in

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features of peptide binding to MHC molecules

  • each MHC molecule displays one peptide at a time

  • low affinity, broad specificity → many different peptides can bind to the same MHC molecules

  • very slow off-rate → displays long enough to be located by T cell

  • binds peptides only!

  • do not discriminate between foreign antigens and self antigens

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how does the number of class I MHC molecules differ in heterozygous vs. homozygous offspring?

  • heterozygous = maximum of 6 different class I MHCs → present wider array of peptides

  • homozygous = 3 class I MHCs → may not be able to respond to certain antigens

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what is the pattern of expression for MHC molecules?

co-dominance→ both parental alleles of each MHC gene are expressed

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why is high polymorphism of MHC alleles in a population advantageous?

  • promotes species survival

  • increases variation in susceptibility to pathogens

  • in largely homozygous populations, there can be high susceptibility to certain diseases

11
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how are T cells selected for in the thymus?

  • positive selection for weak recognition of self class I and class II MHC-peptide complexes

  • failure to recognize MHC-peptide complex → apoptosis

  • negative selection against strong recognition of either self class of MHC-peptide complex → apoptosis