Ch. 8 MHC Flashcards
(28 cards)
Describe the structure of class I MHC receptors
◦ Larger 45 kDa glycoprotein α chain ◦ 3 external domains ◦ A transmembrane domain ◦ Cytoplasmic anchor ◦ Smaller 12 kDa β2-microglobulin protein ◦ The α1 & α2 domains form a cleft region that binds an 8–10 amino acid–long peptide fragment ◦ A β sheet forms the floor of the cleft ◦ Two α helices form the walls
Describe the structure of class II MHC receptors
◦ Heterodimeric ◦ A 33 kDa α chain ◦ A 28 kDa β chain ◦ Both chains have transmembrane domain ◦ The α1 & β1 domains form a cleft region that binds an 13-18 amino acid–long peptide fragment ◦ A β sheet forms the floor of the cleft ◦ Two α helices form the walls
What peptide lengths are accommodated in class I MHC?
8-10
What peptide lengths are accommodated in class II MHC?
13-18
What determines whether a peptide will fit into a class I MHC receptor?
o These receptors exhibit polymorphism in the peptide-binding region
Class I MHC-peptide interactions
Peptides derived from endogenous intracellular proteins
Some amino acids are anchor residues that anchor peptide into groove
Other amino acids are available to interact with a cytotoxic TCR
What determines whether a peptide will fit into a class II MHC receptor?
o These receptors exhibit polymorphism in the peptide-binding region
Usually derived from exogenous extracellular processed antigens
Present antigen peptides to CD4+ (helper) T cells
Amino acid interactions along the peptide’s length responsible for binding
Hydrophobic/aromatic residues
Not “anchor residues”, but simple amino acid interactions along the length of the peptide
How did we find out MHC was important?
◦ Peter Gorer discovered in the 1930s four groups of genes that encoded blood-cell antigens in mice (which he designated I-IV)
◦ In the 40s & 50s, researchers found that group II was critical in the rejection of transplanted tumors & other tissues in mice
What does histo mean?
greek “histos” for tissue
What are the three major classes of proteins coded for in MHC loci?
- Class I MHC genes
- Class II MHC genes
- Class III MHC genes
What are the MHCI gene products in mice?
o H-2K, H-2D, H-2L
What are the MHC I gene produces in humans?
o HLA-B, HLA-C, HLA-A
What are the MHC II gene products in mice?
IA (aB), IE (aB)
What are the MHC II gene products in humans?
DP (aB), DQ(aB), DR (aB)
Why are MHC alleles predominately inherited as haplotypes?
◦ Because they lie so close together on the chromosome that recombination events during cell division would not separate them
◦ Therefore, inherited as a “set”
Syngeneic
identical at all genetic loci
Congenic
identical at all loci except one region
What experimental protocol can be followed to show that MHC is codominantly expressed by cells?
Mating of inbred mouse strains with different MHC haplotypes
What experimental protocol can be followed to show that MHC is involved in tissue rejection
Skin transplantation between inbred mouse strains with same or different MHC haplotypes
How many different K, D, & L receptors can be expressed by a single nucleated mouse cell?
Mice have three K, D, and L loci
How many total unique MHCI receptors are expressed by nucleated cells of mice?
6 unique receptors to present to Tc cells
How many different A, B, & C receptors can be expressed by a single nucleated human cell?
Humans have 3 (A,B, and C) loci
How many total unique MHCI receptors are expressed by nucleated cells of humans?
6 unique receptors to present to Tc cells
How many total unique MHCII receptors are expressed by mouse APCs?
8 unique receptors to present to Th cells
How many total unique MHCII receptors are expressed by human APCs?
12 unique receptors to present to Th cells
