Main receptors αβ Alpha ampbeta γδ Gammaamp delta Coreceptors CD4ampCD8 molecules Costimulatory receptors CD28 Signal transduction molecules e g d and z chains ID: 509041
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TCR RECEPTORS
Main receptors-αβ(Alpha &beta)- γδ(Gamma& delta)Co-receptors-CD4&CD8 moleculesCo-stimulatory receptors-CD28Signal transduction molecules-e, g, d and z chainsAdhesion & co-stimulation-IntegrinSlide2
αβ(Alpha &beta)
and γδ(Gamma& delta)Majority(>95%) of T cell receptors are αβ1-5% are γδ, role not clearly knownRecognize antigens on MHC’SStructure consist of -1 variable (V) domain -1 Ig-like constant (C) domain -A hydrophobic transmembrane region(T m) -A short cytoplasmic regionSlide3
Genetics
Βγ chains-coded for by gene clusters found on chromosome 7 αδ chains- coded for by gene clusters found on chromosome 14Multiple different V region gene segments are present in each gene clusterOne V region gene segment is assembled and is joined to the constant region gene segment.The mRNA) transcript is spliced and a mature mRNA) transcript is produced which is translated into αδ or Βγ protein chainsNoteThe expression of a complete V–C gene product excludes further rearrangement events
This phenomenon is
referred to as allelic exclusion
(allelic
exclusion)
The
T cell becomes committed to the expression of a single V–C α chain, and a single V–C β chain.Slide4
Visualization of conceptsSlide5Slide6
The TCR CD3 complex
CD3(αβδε) and ζ moleculesThey exist as dimers i.e. -CD3αβ, -CD3eg dimer -CD3ed dimer -CD3zz
dimer
They are non covalently associated with TCR
Play a role in signal
transduction that leads in T cell
activationSlide7
CD4&CD8 co-receptors
Are expressed on the surface of mature T cellsParticipate with TCR receptors in recognition of antigens on MHC hence the name co-receptorsCD4-MHCIICD1-MHCI CD4 is found in helper T cells and CD8 is found in cytotoxic T cellsAbout 65% of mature a positive T cells in the blood and lymphoid tissues express CD4. and 35% express CD8Both consist of 1 extracellular Ig domain, 1hydrophobic transmembrane region, and a 1, highly basic cytoplasmic tail about 25 amino acids long. CD4 has four extracellular
Ig
-like domains, a hydrophobic
transmembrane
region, and a highly basic
cytoplasmic
tail 38 amino acids longSlide8
The two N-terminal
Ig-like domains of the CD4 protein bind to β2 domain of the class II MHC moleculeCD8 molecules exist as disulfide-linked heterodimers composed of two related chains called CD8α and CD8βThe Ig domain of CD8 binds to the non polymorphic α3 domain of class I MHC molecules.Slide9
Co-stimulatory molecules
CD28 recognize co stimulatory molecule B7 found APCs, costimulatory molecules are important in B cell activation