Ch. 9. T-cell receptor

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Ch. 9. T-cell receptor Structure was not
discovered until 1980s harder to resolve than
antibody molecule membrane bound specific for
antigen plus MHC So purification and
description of antigen- receptor interactions
was difficult
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Antigen-specific and signal-transducing complex
?? or ?? antigen-specific receptor CD3
complex Much was learned about how the T cell
receptor worked, before the receptor
was resolved
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p. 224
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How did MHC restriction work? Dual receptor? One
for MHC, one for antigen? Altered-self? One
receptor recognizes the MHC-antigen complex?
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Monoclonal antibodies were used to isolate the
T-cell receptor Looked for clone-specific
antibodies What made it clone specific? Binding
to the T cell antigen receptor
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p. 226
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T cell receptor genes were found by subtractive
hybridization (see p. 225) Membrane-bound
proteins (mRNA in membrane- bound
polyribosomes Obtain T cell-specific cDNA Look
for sequences that rearrange are expressed only
in T cells ? chain was discovered first- then ?,
? and ?
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TCR gene families- four of them V-J
rearrangements of ? and ? chain, V-D-J in others
? chain family is located between V? and J? So
if ? is rearranged, ? is deleted
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p. 229
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p. 230
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Sources of TCR diversity similar to that
seen with Ig Junctional diversity Nucleotide
addition Combinatorial joining Little somatic
mutation in TCRs
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TCR forms a complex with CD3 Monoclonal
antibodies showed that TCR and CD3 are
cross-linked If CD3 is not present, neither is
TCR
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p. 236
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TCR-CD3 is NOT the whole story in T
cell activation! Many accessory membrane
molecules
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p. 237
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p. 237
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p. 239
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(No Transcript)
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Antigen presentation requires self-MHC Cytotoxic
T cells can also be alloreactive (nature of
graft rejection) Can TCR cross-react with
allogeneic MHC? Seen with T cell clones
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Summary T cell receptors react with processed
antigen bound to a self-MHC molecule on
an antigen-presenting cell or target cell MHC
molecules are very polymorphic and can vary in
immune responsiveness CD4 cells are class II
restricted, while CD8 cells are class I
restricted Formation of TCR-MHC-Antigen complex
is required
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T cell receptors are organized into variable and
constant regions and, through gene
rearrangement, have a greater potential
diversity than antibodies T cell receptors is
associated with CD3, and other accessory
molecules are required for T cell activation