MHC Genomic Organization and Structure Flashcards
Characteristics of each class of genes that code for MHC
- Class I MHC genes encode glycoproteins expressed on the surface of nearly all nucleated cells. Function: presentation of peptide antigens to Tc cells.
- Class II MHC genes encode glycoproteins expressed primarily on antigen-presenting cells (macrophages, dendritic cells, B cells), where they present processed antigenic peptides to Th cells. Thymic Epithilial Cells (TEC)
- Class III MHC genes encode secreted proteins that have immune functions s.a Complement system and molecules involved in inflammation.
How do Class I AND Class II structures differ?
Class I
- Peptide binding cleft
- 1 chain (a1, a2, and a3) and a Beta2 microglobin molecule
- I transmembrane segment
- Anchors molecules at both ends of the peptide;generally hydrophobic carboxy-terminal anchor
Class II
- Open socket for peptide binding
- Two chains (a and b)
- 2 Transmembrane segments
- Conserved residues along the length of the peptide
Bare Lymphocyte Syndrome I
Tap 1 and 2 deficiences
Prevents the formation of peptide : HLA I complex
HLA class I not expressed on the membrane
CIITA (class II transactivator)
a protein that interacts with and stabilizes the RFX complex but does not bind to the MHC class II gene promoter itself.
How many amino acids are found in the alpha chains of the MHC Class I molecule?
Approximately 90
What is the nature of the bound peptide in MHC Class I? Class II?
Class I (Extended structure in which both ends interact with the MHC molecule but the middle arches away from the MHC molecule
Class II (Extended structure that is held in constant elevation above the floor of the MHC groove
What type of inheritance does MHC express?
Codominance
Regions and Gene Products of CLASS II
Regions: DP, DQ, DR
Gene Products: DP alphabeta, DQ alphabeta, DR alphabeta
Mutations of which genes can cause BLS II?
RFX
CIITA
MHC genes are highly ______________
polymorphic.
When can T cells recognize an antigen?
Once it has been processed and presented in the context of molecules encoded by MHC
The MHC is referred to as the _________ complex in humans and the _________ complex in mice.
HLA; H-2
Allelic forms of MHC genes are inherited in linked groups called ____________
haplotypes.
In which order are gene classes expressed on the HLA complex?
II, III, I
The major histocompatibility complex is a collection of genes arrayed within a long continuous stretch of DNA on chromosome__________ in humans and on chromosome_________ in mice.
6; 17
Class II MHC molecules contain two different polypeptide chains, a ____________ α chain and a ___________ β chain, which associate by ___________interactions
33-kDa; 28-kDa; noncovalent
The ability of an individual class I MHC molecule to bind to a diverse spectrum of peptides is due to ____________
the presence of the same or similar amino acid residues at key positions along the peptides.
Regions and Gene Products of CLASS I
Regions: B,C,A
Gene Products: HLA-B, HLA-C, HLA-A
Wat four factors regulate MHC expression?
- Transcription factors
- Cytokines
- Interferon Gamma :induce the formation of a specific transcription factor that binds to the promoter sequence flanking the class I and II MHC genes
- IL-4; Increases expression of class II molecules by resting B cells.
_____________molecules expressed by an individual influences the repertoire of antigens to which that individual’s T cells can respond
MHC
RFX (regulatory factor X)
forms a complex that binds to the promoter of the MHC class II gene; the fourth factor
Role of MHC
- Play roles in intercellular recognition and in discrimination between self and nonself.
- Participates in the development of both humoral and cell-mediated immune responses.
What are the clinical manifestations of BLS?
- infections of the respiratory or the digestive tract.
- Absence of antibody formation and the absence of cell-mediated response.
- Necrotizing granulomatous skin lesions.
- Chronic inflammation of the upper respiratory tract include lethal midline granuloma (LMG)
- Chronic sarcoidosis
Nonclassical gene products
Expression of the class I HLA-G molecules on cytotrophoblasts at the fetal-maternal interface.
HLA-G may play a role in immune tolerance in pregnancy.
HLA-G is a ligand for NK cell inhibitory receptor KIR2DL4, and therefore expression of this HLA by the trophoblast defends it against NK cell-mediated death
Bare Lymphocyte Syndrome II
Mutation in genes that regulate the expression of MHC II genes
Treatment: Bone marrow transplantation
Regions and Gene Products of CLASS III
Region: C4, C2, BF
Gene Products: C- Proteins, TNFa, TNFbeta
Which MHC class includes complement proteins?
MHC Class III
•The α1 and α2 domains interact to form a platform of _________ antiparallel β strands spanned by ________long α-helical regions.
eight;two
Both class I and class II MHC genes are flanked by 5’ promoter sequences that bind____________
transcription factors
•Class I MHC molecules contain a____________ (kDa) α chain associated noncovalently with a __________β2-____________ molecule.
45-kilodalton; 12-kDa; microglobulin
Amino acids at positions ______,________ and ___________ are considered anchor residues.
2, 3, and 9
What size peptide can bind to the cleft of MHC class II molecules?
13-18 aa
The peptide-binding region is located on the surface of the MHC I molecule and is able to bind a peptide of _________ to _________amino acids.
8;10
