L5: AR - T Cell Recognition

what do t cells recgonise

short peptide fragments presented on MHC molecules

how is t cell recognition different from b cells

b cells recognise whole antigens while t cells only recognise processed peptides on MHC

what is the TCR

antigen receptor on t cells

what is the structure of the tcr

heterodimer of a and b chains (most common)

what alternative tcrs exist

yo TCR (less common)

what regions do tcr chains have

variable and constant

what complex is required for TCR signalling

CD3 complex

can TCR signal on its own

no, it requires CD3

what is MHC

molecules that present peptides to t cells

what is MHC called in humans

HLA - human leukocyte antigen

where is MHC class I found

all neucleated cells

what type of antigens does MHC I present

endogenous (intracellular e.g. viruses)

which t cells recognise MHC I

CD8+ cytotoxic t cells

what molecule is required for MHC I stability

b2-microglobulin

where is MHC class II found

professional APCs (DC, macrophages, B cells)

what type of antigens does MHC II present

exogenous (extracellular)

which t cells recognise MHC II

CD4+ helper T cells

difference between MHC I and MHC II

i - intracellular, CD8

ii - extracellular, CD4

where do peptides bind on MHC

peptide binding groove

what is the structure of the MHC groove

2 a helices and b sheet floor

how does tcr recognise antigens

recognises peptides and MHC complex - dual recognition

what is the endogenous pathway

processing of intracellular antigens (viral proteins)

where are proteins degraded

cytoplasm (proteasome)

how do peptides enter the ER

via TAP transporter

where do peptides bine MHC I

endoplasmic reticulum

what happens after protein binds to MHC I

MHC I + peptide → cell surface

which t cells respond

CD8+ t cells that kill infected cells

what is the exogenous pathway

processing of extracellular antigens

how are antigens taken up

phagocytosis/endocytosis

where are proteins degraded

edosome/lysosome

what blocks MHC II in ER

invariant chain

why is the invariant chain important

prevents premature peptide binding

what happens to the invariant chain

degraded in acidic compartment

where do peptides bind MHC II

endosomal compartment

what happens after peptides bind to MHC II

MHC II + peptide → surface → activates CD4 T cells

what is cross presentation

exogenous antigen presented on MHC I

what is autophagy

endogenous antigen presented on MHC II

what does polymorphism mean

many different MHC alleles in population

why is MHC polymorphism important

allows recognition of many different peptides

why is MHC important in transplantation

differences cause graft rejection

is tcr binding alone enough for activation

no, also requires costimulation

examples of costimulatory interaction

CD28 (T cell) binding to CD80/86 (APC)

what do cytokines from APCs do

influence t cell activation

what s CTLA-4

inhibitory receptor on T cells

what is PD-1

inhibitory checkpoint receptor

what are the key steps in T cell antigen recognition

1. antigens processed into peptides

2. peptides presented on MHC

3. tcr recognises peptide-MHC

4. costimulation activated t cell