T Cells, Effector Functions & the MHC #1 Flashcards
What does TCR recognise?
foreign mol bound to self protein
What do T cells display?
peptides derived from foreign antigens in context of highly polymorphic MHC mol
What is structure of MHC I?
- single chain
- ass non-covalently with beta 2 microglobulin
Where does MHC I express?
endogenously derived peptides on all nucleated cells (currently being syn in that cell)
What is structure of MHC II?
- alpha beta heterodimer
Where does MHC II express?
- peptides from exogenous antigens taken up by receptor mediated uptake/endo fro outside on specialised APC
List APC ass with MHC II
- monocytes
- macrophages
- DC
- B lymphocytes
What is function of MHC mol?
display foreign peptides to T cells
What does peptide consist of?
8-15 aa
What happens when virus infects cell?
hijacks host cell’s protein production machinery in order to replicate
How does MHC I present peptides?
- host cell break down sample of all proteins currently being made in cell using proteosome mol
- take peptides + transport to ER where loaded into newly syn MHC I
- loaded to cell surface, displaying peptides to immune system
What can the MHC I show?
- sample of all proteins being made in cell at the time
- mostly normal self-proteins which immune system ignores
- sometimes show peptides derived from viral antigens
How does MHC II present peptides?
- DC takes up antigen by endo
- vesicles contain protelytic enz which degrade peptide
- MHC II syn + assembled in ER + migrate to late endosomes + fuse with vesicles
- peptides loaded into MHC II mol which are transported to cell surface
Where are genes encoding MHC I + II found + sig?
- on short arm of Chr 6
- aka human leukocyte antigen
- most polymorphic/genic region of human genome - sev MHC I + II genes encoding sep mol
How many + what are genes encoding MHC I?
- 3 genes encoding for 3 diff but related HLA proteins (HLA-A, B + C)
How many + what are genes encoding MHC II?
3 pairs of genes encoding for 3 diff HLA class II mol (HLA-DR, DQ + DP)
Why is genes of MHC mol being highly polymorphic sig?
- many diff alleles/variants of each gene exist within pop
- 600+ alleles/variants of HLA I-B
- great diversity of HLA proteins on cell surface of human pop
unlikely 2 indiv display same HLA mol on APCs
How are genes of MHC mol inherited?
- co-dom expressed
- inherit 1 allele from M + F - express both
Where are polymorphisms in HLA found?
aa that form peptide binding groove
What do aa that form peptide binding groove determine?
which peptides from foreign antigen presented to immune system
What is polygenic + polymorphic nature of HLA sig for?
- make it imposs for pathogen to evolve antigen that can’t bind to any HLA mol + so can’t trigger immune response
- as diff HLA in pop, always at least 1 mol that can bind any peptide from antigen of any pathogen
What are T cells defined by?
expression of TCR
Describe structure of TCR
- mem-bound heterodimer
- 2 chains encoded by diff genes joined by disulphide bonds
- 2 subtypes (1-alpha + 1-beta chain) + (1-gamma + 1-delta chain)
- consist of variable + constant domains
What do TCR undergo?
rearrangements from germline before translation from 1 config expressed in each cell