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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.