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Review
. 2001 Jun 19;98(13):7461-8.
doi: 10.1073/pnas.131202998. Epub 2001 Jun 5.

How the immune system works to protect the host from infection: a personal view

Affiliations
Review

How the immune system works to protect the host from infection: a personal view

C A Janeway Jr. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Figure 1
Figure 1
Various pathogen-associated molecular patterns recognized by cognate pattern recognition receptors expressed on APCs induce the expression of B7 molecules, which signal the presence of pathogens and allow activation of lymphocytes specific for antigens derived from the pathogens. Shown are lipopolysaccharide recognition by TLR-4, proteoglycan recognition by TLR-2, and the recently reported role of TLR-9 in the recognition of CpG DNA.
Figure 2
Figure 2
Demonstration that the binding of the TCR to agonist peptides induces dimerization of TCRs, leading to two TCRs binding stably to one peptide: MHC class I molecule, whereas antagonist peptides that induce positive selection lead to binding but not TCR dimerization. The results with agonist peptide can be seen only at 37°C and not at 25°C. Data from Alam et al. (29).
Figure 3
Figure 3
My personal interpretation of the results reported by Alam et al. (28), showing the dimerization to the TCR when one is bound to an agonist peptide and the other is bound to a self-peptide in its native conformation.
Figure 4
Figure 4
Data derived from in vivo positive and negative selection as interpreted by the experiments shown in Figs. 2 and 3. Shown are T cell receptors binding to agonist peptides and to antagonist peptides. The agonist peptides used to bind to the TCR induce dimer formation, but only in the presence of self-peptides, leading to activation followed by deletion in the thymus (panel 1). Y-Ae analogue peptide, which can positively select thymocytes, causes binding but not deletion. These self-peptides do not induce dimer formation, although they bind to the TCR. As a result of binding, these peptides induce positive selection in the thymus and sustain T cells in the periphery (27). Panel 3 shows what happens when the TCR does not bind to any peptide, leading to death by neglect. Our favored interpretation of the paradoxical positive selection seen with covalently linked agonist peptide in the absence of invariant chain and the endogenous I-Aformula image (panel 4) shows that all of the TCRs on a thymocyte adopt the same conformation and thus cannot aggregate, leading to positive selection. See text for further details.

References

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