t cell receptor
DESCRIPTION
T Cell Receptor. Hugh B. Fackrell Nov 9, 1998. T Cell Receptor. Assigned Reading Content Outline Performance Ojectives Key terms Key Concepts Short Answer Questions. Assigned Reading. Chapter: 11 pp 264-283 Janis Kuby’s Immunology 3rd Ed. Early Studies Structure of T cell Receptors - PowerPoint PPT PresentationTRANSCRIPT
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T Cell Receptor
Hugh B. FackrellNov 9, 1998
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T Cell Receptor Assigned Reading Content Outline Performance Ojectives
– Key terms– Key Concepts
Short Answer Questions
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Assigned Reading Chapter: 11 pp 264-283 Janis Kuby’s Immunology 3rd Ed
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Content Outline Early Studies Structure of T cell Receptors TCR Genes Cloning TCR multi gene families T Cell Receptor Complex TCR-Peptide-MHC Complex Associative recognition hypothesis Formation of ternary complex Alloreactivity of T Cells
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Early Studies self MHC restriction isolation of t cell receptors
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Independent vs Associative Recognition by
T cells
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Evidence for Altered Self Model
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TCR: Structure Hetero dimer
– 95% Alpha: Beta– 2-5% Gamma:
Delta Variable Domains
– 3 HVR Constant Domains
Transmembrane region (Tm)– ~20 AA
Cytoplasmic Tail (CT)– 5-12 amino acids
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Structure of T cell Receptors
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Cloning TCR Genes
DNA subtractive hybridization
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TCR Genes
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TCR multi gene families: Outline
Variable region rearrangements TCR DNA rearrangements Allelic exclusion Structure of rearranged TCR genes Generation of TCR diversity
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TCR Multigene Families: General
4 multigene families one for each chain Gene rearrangements
– Alpha: Gamma - V J exons– Beta: Delta - V D J exons
Chain exclusion
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TCR Gene Rearrangement
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TCR vs Ig
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T Cell Receptor Complex CD4 & CD8 coreceptors Accessory membrane molecules
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TCR-Peptide-MHC Complex
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Associative recognition hypothesis
Formation of ternary complex Affinity of TCR Peptide topology
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Alloreactivity of T Cells
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Performance Objectives
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Key Terms CD2, CD4, CD8, CD28, CD54,
CD58, integrins, T cell receptors, alpha beta TCR, gamma delta TCR,
Transcription factor NF-KB
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Key Concepts Draw the structure of the T Cell
Receptor (TCR) Compare and constrast the structure of
TCR with B cell receptor Draw a diagram of the T cell receptor
gene organization
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Describe the stragetgies for diversification of T Cell Receptors
Describe how a T cell Receptor recognizes an antigen
Describe the TCR-Antigen-MHC complex
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Short Answer Questions
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Hedrick and Davis used the technique of subtractive hybridization to isolate cDNA clones encoding for the T cell receptor. – Briefly explain the method of subtractive
hybridization.– State why this method was so important
in the characterization of the TCR.
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What does it mean to say that TCRs belong to the Ig supergene family?
Briefly describe the heterodimeric structure of the TCR.
TCR genes use the same strategies as antibody genes to develop receptor diversity; however, TCR genes do not exhibit somatic hypermutation. Why?
The TCR is closely assoicated with another surface protein complex. What is its name and function?
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Describe the three way complex that occurs during antigenic recognition by T cells.
T cells can react only with protein fragments. – What is this process called?– How does it occur?
Which pathway leads to antigen interaction with MHC-I molecules?
Which pathway leads to interaction with MHC-II molecules?
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What are accessory molecules? – Give some examples.– Briefly discuss how they may be
involved in antigen recognition by T cells.