1. The T-Cell Receptor Folder title: Receptor MHC Restriction
TCR Structure & Function
Genetic Generation of TCR Diversity
Thymus T-cell "Education" and Immunological Tolerance
Folder: Receptor
The specific adaptive immune response is directed by four major components: (1) antigen being presented, (2) an MHC Class II protein presenting the antigen, (3) cytokine and cytokine receptor signalling, and (4) a specific T-cell receptor that recognizes the Class II MHC protein and the antigen being presented.
We have already covered antigens, cytokines, and MHC proteins. This next subject in the course will deal with the fourth participant, the T-cell Receptor (TCR).
Folder title: Receptor
November 15, 2006
TCRTitle

2. Comparison of T-Cell Receptors (TCR) and Antibodies: Differences
Remains Membrane-bound.
Present in small amounts.
Recognizes binary complex:
Antigen and MHC Protein
Associated with CD3, CD4, & CD8 AccessoryMolecules
Is MHC Restricted
Antibody
Can be membrane bound;
Secreted in large amounts.
Recognizes Antigen alone:
Soluble or particulate
No accessory molecules
involved
Not MHC Restricted
Folder: Receptor
Antibodies and TCR's have the same functional role to play. They both recognize specific antigens. In some ways they are similar to one another. These similarites are shown on the next slides. In some ways, Ab's and TCR's are different in how they recognize antigens. These differences are shown here.
TCRvsAb1

3. Comparison of T-Cell Receptors (TCR) and Antibodies: Similarities
TCR and Ab
Rearrange V, J, and (Sometimes) D Germ-line Genes, link these, and join them to C-region Genes, during somatic cell differentiation.
(V, J, D and C region germ-line genes are different for TCR vs Ab)
Have Complementarity Determining Regions (CDR's) that are hypervariable
Recognize an enormous variety of antigenic determinants
Folder: Receptor
Antibodies and TCR's have the same functional role to play. They both recognize specific antigens. In some ways they are similar to one another. These similarites are shown on this slide. In some ways, Ab's and TCR's are different in how they recognize antigens. These differences were shown on the previous slide
TCRvsAb2

4. See Figure 8-15, Kuby, 6th Edition p. 207 Folder: Receptor
Cytotoxic T-cells are sensitized in an animal exposed to an exogenous pathogen, in this case an LCM virus. The sensitized T-cells will recognize and lyse LCM-virus-infected target cells in an assay done in cell culture. However, the TCL (cytotoxic T-lymphocytes) will recognize only LCM virus-infected cells, and they will recognize only LCM-virus-infected cells of the same MHC haplotype that they were sensitized to. This means that they will recognize only LCM-virus-infected self-cells (or those from mice with the same haplotype). They will not recognize LCM-virus-infected allogeneic cells. Thus they are "MHC-restricted", they recognize the antigen only in the context in which they saw it when being sensitized.
Remember, radioactively-labelled Chromium (Cr) is used to determine when a cell has been killed because it leaks out of dead cells.
See Figure 8-15,
Kuby, 6th Edition
p. 207

5. MHCRestr Self-MHC Restriction of TCR
Folder: Receptor
The TCL shown on the previous slide are restricted to recognize antigen only in the context of the MHC haplotype that they saw when first exposed to the antigen. They are also specific only for the original antigen. Thus TCL specific for an LCM virus antigen will not recognize and influenza virus antigen whether it is presented on a self-MHC protein or not.
MHCRestr
Self-MHC Restriction of TCR
Kuby, 6th Edition, Fig 9-1, p. 224

6. Figure 10-5. Top. Kuby, 6th Edition, p. 249

7. Figure 10-5. Bottom. Kuby, 6th Edition, p. 249

10. See Figure 9-3, Right Side, Kuby, 6th Edition, p. 226

15. (costimulates)
costimu
(inhibits)

16. Generation of Alpha and Beta Subunits of TCR from Germ-line DNA Figure 11-6, Kuby 3rd Edition

17. See Table 9-3, Kuby, 6th Edition, p. 229

22. Allo-Reactivity of T-Cells: or Why Do T-cells Frustrate Transplant Surgeons?
Figure 11-1
Kuby, 3rd Edition
AlloKill