lecture 14/15 - major histocompatibility complex Flashcards
Describe the importance of MHC, how do they accomplish this?
Immunity → antibody and cell mediated immune response
Transplantation → graft rejection
Disease → relative risk factor is high with certain MHC allele
They bind and present antigenic peptides on the surface of cells for recognition by T-lymphocyte receptors
What is the concept of dual specificity in relation to T cell receptor recognition?
They recognize polymorphic residues of self-MHC molecules, which accounts for their MHC restriction
Recognizes residues of peptide antigens displayed by these MHC molecules which are responsible for their antigen specificity
What is non-specific T cell activation?
Bacterial superantigens bind MHC-II (not class 1!!) and TCR and stimulate CD4-T cells non specifically
Describe the distribution of Class I molecules
Expression on all nucleated cells, most highly in non-RBC hematopoietic cells
Bind and present peptides derived from endogenously synthesized proteins in the cell to T cells
3 alpha chain domains - 1, 2 and 3
1 and 2 fold together to form peptide binding cleft
Heterodiner of alpha chain which is covalently associated with a beta-2-microglobulin
Beta-2 not encoded within the MHC complex
CD8 → binds to alpha 2 and 3
dwscribe the expression of class II molecules
Expression detected on surface of professional antigen presenting cells ie dendritic, B and macrophages
Bind and present peptides derived from exogenous proteins that have entered the cell by phagocytosis or endocytosis to the T cells
Heterodimer of 2 alpha domains (1+2), covalently bonded to beta chain (1 and 2)
Peptide binding cleft formed by folding of alpha and beta 1
Ability for alpha chain from one locus to pair with a beta chain from another
CD4 → binds to beta 1 and 2
What is responsible for the diversity of antigen binding abilities amongst alleles?
Polymorphism of the MHC class I and II molecules → results in differences in amino acid sequences and thus a diversity of Ag binding abilities
Polymorphism of the MHC class I and II molecules → results in differences in amino acid sequences and thus a diversity of Ag binding abilities
Encode other proteins that function in immunits like cytokines and complement proteins
What is the HLA/H2-DM molecule?
Special class of MHC class-II molecules not expressed on the cell membrane but found predominantly in specialized endosomal compartment Helps in peptide binding to MHC-II molecules during the final steps of antigen processing inside the endosomal compartment
What are CD cells and how are they important for TCR-MHC interactions?
Cluster of differentiation cells, defining a cell-surface molecule recognized by a unique monoclonal antibody
T-cell co-receptors that bind MHC to aid in signal transduction and are important in the selection of T cells in the thymus
How do CD4 and CD8 differ?
CD4 is a monomer with 4 extracellular Ig domains
CD8 is a heterodimer with disulphide linked alpha and beta chains
describe the binding cleft of MHC class I
Made up of alpha 1 and 2 domains folded over beta sheets
Ends of bound peptide buried is about 8-10 amino acids long
Polymorphic variation restricted to the alpha 1 and 2 domains
describe the peptide bidnign cleft of MHC class II
Made of of alpha and beta 1 domains
Ends of peptide are not buried and are 13-18 amino acids long
Polymorphic variation restricted to the 1 domains
contrast human and mice MHC
human: Major class I loci are A,B and C Major class II loci are DP,DQ and DR
mice: Major class I loci are K,D and L MAjor class II loci are IA and IE
What is a haplotype and why are they relevant to MHC?
The set of alleles inherited from the parents
Both alleles are expressed and the product of both alleles are found on all expressing cells, meaning expression is co-dominant
F1 cells express the MHC proteins from both parents and are therefore histocompatible with both parents
F1 progeny is able to accept grafts from either parent because it recognizes the parental MHC as self
Neither parent can accept graft from progeny because it will recognize the other F1 as foreign
