L5 - Antigen recognition: T cells

what is the equivalnet of antibody on T cell

T cell receptor (TCR)

How do they look TCR

• have variable region at top

• constant region

• Have alpha and beta chains for Alpha- Beta T cells → most common (also gamma-delta T cells)

• trasnmembrane like in BCR

Key difference between BCR and TCR

BCR at some point can change into plamsma cell and then secreate its antibody (when B cell secreates receptor its now called antibody)

TCR cannot do this - stays in transmembrane region

• both start as tarsnmemebrane

How do we get diversity in TCR

• Multiple germ line genes

• V-j and VDJ recombination

• recombination inaccuracies

• Nucleoidal addition by TdT

• Chain combinations - not as much as only a and b chain

(so somatic hypermutation)

What are the chains found on antbody, TCR ab and TCR gd

Diffrences between B cell and T cell - cell recognition

B cell

• Varibale region of both heavy and light chain bind to antigen, proetin protein interaction

T cell

• TCR binds to linea peptides (small) that have been presented by MHC

MHC

• 2 differnet types 1 and 2

• Both are bound to cell surface - base extends through memebaren into cell to hold it in pace

• allow holding of peptide to present to TCR

  • MHC has 2 subunits called Alpha and beta → looks similar to MHC1 but both have different jobs

MHC binding groove

• have 2 alpha helicase iwth channel inbetween where peptide sits

• space for peptide with 9 - 12 amino acids

• groove allows stablisazation of peptide

• MHC1 → groove slightly closed → smaller peptides

  • MHC2 → more open → longer peptides

MHC TCR bidning

• TCR has CDRs like in B cells

• TCR has conserved regiosn that bind to MHC

• CDR3 binds to peptide → where VDJ all overlap - most diverse part

How can MHC bind to multiple peptides

• binds to main chain of peptides - shared across all peptides

• some special MHCs binds to peptides that have tweird twists in them

Different types of MHC

• class 1 , 2

• non classical 1, 2

• class 3 → not alwyas immunological

Genes that code for MHC

MHC1

• A

• B

• C

MHC2

• DQA1

• DQB1

• DPA1

• DPB1

• DRA

• DRB1

What is the 2 pathway model for antigen presentation in T cells

Exogenous pathway

Endogenous pathway

How do tumours change

• they downregulate MHC1 so not recognised by CD8 cells

how do viruses interfere with antigen presnettaion

usually have protein thats whole job is to interphere with this process as aloows them to grow and rpelicate without being detected by immune system

CD3

• have acessory proetins that come to help amplify signal between TCR and MHC peptide molecuel

• done through T cell reptor complemx called CD3 made up of delpta, gamma and zelta amplify signal

• CD4 not associated with CD3 complex

what else do we need for activation

need co stimulattion, good blance between positve and negtaive signal to tell T cell repseptor to respond