T Cell Receptor

The things taught in colleges and schools are not an education,
but the means of education
Ralph Waldo Emerson

Who am I?: I was awarded the Nobel Prize in 1984 for my theoretical studies on the immune system. I developed the concept that the thymus is the site where lymphocytes multiply differentiate and become functional T cells.

RESOURCES

ASSIGNED READING

CHAPTER 11: pp 264-283

OUTLINE/SUMMARY

1. Early Studies
   • self MHC restriction
   • isolation of t cell receptors
2. Structure of T cell Receptors
3. TCR Genes
   • Cloning
   • TCR multi gene families
   • Variable region rearrangements
   • TCR DNA rearrangements
   • allelic exclusion
   • Structure of rearranged TCR genes
   • Generation of TCR diversity
4. T Cell Receptor Complex
   • CD4 & CD8 coreceptors
   • Accessory membrane molecules
5. TCR-Peptide-MHC Complex
   • Associative recognition hypothesis
   • Formation of ternary complex
   • Affinity of TCR
   • Peptide topology
6. Alloreactivity of T Cells

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING TERMS

ON COMPLETION OF THIS SECTION THE STUDENT SHOULD BE ABLE TO:

1. Draw the structure of the T Cell Receptor (TCR)
2. Compare and constrast the structure of TCR with B cell receptor
3. Draw a diagram of the T cell receptor gene organization
4. Describe the stragetgies for diversification of T Cell Receptors
5. Describe how a T cell Receptor recognizes an antigen
6. Describe the TCR-Antigen-MHC complex

QUESTIONS

1. Hedrick and Davis used the technique of subtractive hybridization to isolate cDNA clones encoding for the T cell receptor.
2. Briefly explain the method of subtractive hybridization.
3. State why this method was so important in the characterization of the TCR.
4. What does it mean to say that TCRs belong to the Ig supergene family? Briefly describe the heterodimeric structure of the TCR.
5. TCR genes use the same strategies as antibody genes to develop receptor diversity; however, TCR genes do not exhibit somatic hypermutation. Why?
6. The TCR is closely assoicated with another surface protein compolex. What is its name and function?
7. Describe the three way complex that occurs during antigenic recognition by T cells.
8. 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?
9. What are accessory molecules? Give some examples.
10. briefly discuss how they may be involved in antigen recognition by T cells.