TCR and MHC Flashcards
What encodes TCR polypeptides?
Rearranging gene segments (V, D, J) during T cell development in the thymus.
What mechanisms are involved in TCR gene rearrangement?
Similar to Ig gene rearrangement.
Uses recombination signal sequences (RSS) and enzymes (RAG-1/2).
How does TCR diversity arise?
- Multiple V, D and J gene segments
- Combinatorial diversity between V, D and J segments
- Junctional diversity during gene joining
What is a key difference between TCR and BCR?
TCR is never secreted.
No somatic hypermutation (SHM) occurs in TCR genes.
Where are MHC molecule genes located in humans?
Chromosome 6 (HLA complex).
How are MHC molecules expressed?
Co-dominantly.
Which cells express MHC class I molecules?
All nucleated cells.
Which cells express MHC class II molecules?
Antigen-presenting cells (APCs), e.g., B cells, macrophages, dendritic cells.
How can MHC class II expression be induced?
By interferons during inflammation.
Why are MHC genes highly polymorphic?
Allows binding of a vast range of peptides.
Provides an evolutionary advantage by enabling responses to diverse pathogens.
What are the downsides of high MHC polymorphism?
- Increased risk of immune-mediated diseases (e.g., autoimmune diseases).
- Reduced pool of available donor organs for transplantation.
How many different MHC molecules can an individual express?
Class I: Up to 6 molecules (HLA-A, HLA-B, HLA-C; heterozygous at each locus).
Class II: Up to 6 molecules (HLA-DP, HLA-DQ, HLA-DR; heterozygous at each locus).
What types of antigens are presented by MHC molecules?
MHC class I: Endogenous antigens (e.g., viral proteins).
MHC class II: Exogenous antigens (e.g., bacterial proteins).
How are endogenous antigens processed for MHC class I?
- Synthesised in cytoplasm
- Cleaved into peptides by proteasome
- Transported to ER by TAP transporter
- Loaded onto MHC class I
- MHC-I/peptide complex transported to cell surface
What proteins are involved in the MHC class I pathway?
Proteasome
TAP transporter
Tapasin and calreticulin (peptide-loading complex)
How are exogenous antigens process for MHC class II?
- Endocytosed into vesicles
- Cleaved by acid proteases in vesicles
- Vesicles fuse with MHC class II-containing vesicles
- Peptides loaded onto MHC class II
- MHC-II/peptide complex transported to cell surface
What prevents premature binding of peptides to MHC class II in the ER?
Binding of the invariant chain to the groove
How are peptides loaded onto MHC class II?
Invariant chain is degraded in the endocytic pathway, leaving CLIP in the groove.
HLA-DM facilitates displacement of CLIP and loading of antigen-derived peptides.
What is unique about BCR and TCR diversity?
Diversity within an individual.
Genes formed by rearranged segments joined imprecisely.
Clonally distributed (each B/T cell has a unique BCR/TCR)
What is unique about MHC class I and II diversity?
Diversity at the population level.
Limited number of forms in an individual.
Polymorphic residues affect peptide-binding, enabling presentation of diverse peptides.
Which cells are specialised APCs?
Macrophages
Dendritic Cells
B cells
How do APCs activate T cells?
Present extracellular antigens on MHC class II to helper CD4+ T cells
What is the role of non-APC cells in antigen presentation?
Express MHC class I and present intracellular antigens to cytotoxic CD8+ T cells
What accessory molecules are involved in the MHC class I pathway?
TAP and LMP
What accessory molecules are involved in the MHC class II pathway?
HLA-DM
