Major Histocompatibility Complex Flashcards
What is the function of MHC?
- marks host cells as self
- antigen presentation to induce an immune response
What are HLA?
Human Leukocyte Antigens = MHC specific to humans
What are the types of HLA loci?
Class I = ABC
Class II = D (DP, DQ, DR)
Class III
Describe the function of Class I HLA molecules.
- located on the surface of all nucleated cells to serve as a “self” marker
- present peptides to CD8+ killer T cells
Describe the function of Class II HLA molecules.
- located on the surface of antigen presenting cells (dendritic cells, monocytes, macrophages, B cells)
- present peptides to CD4+ helper T cells
What is unique about surface markers of antigen presenting cells?
express both Class I and Class II MHC molecules
Compare mouse and human MHC genes.
similar structures and functions
Describe the gene structure of MHC genes.
- all MHC genes are located on chromosome 6, except for B2-microglobulin invariant chain for Class I molecules
- Class II is located 5’ to Class I
- gene products are shuttled to the ER for association with the peptide and then shuttled to the surface
Describe the structure of the final MHC Class I gene product.
- all 3 class I loci code for an alpha chain (3 domains)
- B2-microglobulin chain from another chromosome is invariant and associates with the alpha chain
Describe the domains of a Class I MHC.
alpha 1 and alpha 2 form a peptide-binding cleft
- 2 alpha helices
- 2 beta pleated sheets for a platform for the peptide
alpha 3 anchors the alpha chain to the membrane
B2 domain is a beta pleated sheet
Describe the structure of the final MHC Class II gene product.
- each class II loci codes for an alpha chain and a beta chain (DPalpha and DPbeta)
- alpha chain (2 domains) and beta chain (2 domains) associate together at the surface
Describe the domains of a Class II MHC.
- alpha 1 and beta 1 form the peptide-binding cleft
- alpha 2 and beta 2 have transmembrane portions to anchor them to the cell
What is the difference in peptide binding between class I and class II?
class I binds to shorter peptides (8-10 AA), while class II binds to longer peptides (13-17 AA)
What is the purpose of anchor sequences?
- provide conserved AA regions for the peptide to associate with peptide-binding cleft
- by burying the anchor sequence onto the peptide cleft, the varying AA sequences are available for recognition by TCR
What are the class I anchor sequences?
- C terminal
- Tyrosine
- Hydrophobic AA
- N terminal
What are the class II anchor sequences?
- C terminal
- hydrophobic AA
- negative charged
- basic
- hydrophilic AA
- N terminal
Describe the genetic expression of MHC genes.
co-dominant
- both maternal and paternal haplotypes are expressed
- example: for a host cell, you would have both maternal and paternal alleles/chromosomes expressed for HLA-ABC
- example: for an APC, you would have both maternal and paternal allele/chromosomes expressed for HLA-ABCD
Describe the polymorphic property of MHC genes.
For each MHC locus, there are over 800 possible alleles. Hence, between individuals in a population, there is a high variability in nucleotide sequence => high variability in AA sequence
Where are MHC polymorphisms typically located on the final gene product? What function does this serve?
- located on the peptide-binding cleft at specific sites
- high variability in MHC gene products => ability to bind many different peptides
Define MHC Restriction.
TCR must recognize the peptide AND the MHC molecule (via alpha helices)
What part of the TCR recognizes the MHC?
CD4 or CD8 binds to TCR as a coreceptor to recognize their associated MHC (class II and I, respectively)
List the steps involved after TCR-CD8+ recognizes a peptide-MHC complex.
- recognition
2. kills cell (cytotoxic)
List the steps involved after TCR-CD4+ recognizes a peptide-MHC complex.
- recognition
2. produces cytokines (helper T)
