Why do living trees not rot Redwood trees, for example, can live for centuries, but once

T cells whose receptors strongly bind a self-peptideMHC complex are killed off in peripheral lymphoid organs when they encounter the self peptide on an antigen-presenting dendritic cell.

To guarantee that the antigen-presenting cells in the thymus will display a complete repertoire of self peptides to allow elimination of self-reactive T cells, the thymus recruits dendritic cells from all over the body

The antibody diversity created by the combinatorial joining of V, D, and J segments by V(D)J recombination pales in comparison to the enormous diversity created by the random gain and loss of nucleotides at V, D, and J joining sites.

Why do living trees not rot? Redwood trees, for example, can live for centuries, but once they die they decay fairly quickly. What might this suggest?

It would be disastrous if a complement attack were not confined to the surface of the pathogen that is the target of the attack. Yet, the proteolytic cascade involved in the attack liberates biologically active molecules at several steps: one that diffuses away and one that remains bound to the target surface. How does the complement reaction remain localized when active products leave the surface?

Based on its sequence similarity to Apobec1, which deaminates Cs to Us in RNA, activation-induced deaminase (AID) was originally proposed to work on RNA. But definitive experiments in E. coli demonstrated that AID deaminates Cs to Us in DNA. The authors of the paper expressed AID in bacteria and followed mutations in a selectable gene. They found that AID expression increased mutations about fivefold above the background level in the absence of AID expression. More importantly, they found that 80% of the induced mutations were GA or CT. Does this fit with your expectation if AID-induced mutations arose by deamination of C to U in the DNA?

For many years it was a complete mystery how cytotoxic T cells could see a viral protein that seemed to be present only in the nucleus of the virus-infected cell. The answer was revealed in a classic paper that took advantage of a clone of T cells whose T cell receptor was directed against an antigen assoicated with the nuclear protein of the 1968 strain of influenza virus. The authors of the paper found that when they incubated high concentrations of certain peptides derived from the viral nuclear protein, the cells became sensitive to lysis by subsequent incubation with the cytotoxic T cells. Using various peptides from the 1968 strain and the 1934 strain (with which the cytotoxic T cells did not react), the authors defined the particular peptide responsible for the T cell response (Figure Q241). A. Which part of the viral protein gives rise to the peptide that is recognized by the clone of cytotoxic T cells?

Working out the rules by which T cells interact with their target cells was complicated. Some of the key observations came from studying the way cytotoxic T cells killed cells infected with choriomeningitis virus (LCMV). Cytotoxic T cells derived from mice expressing k-type class I MHC proteins lysed LCMV-infected cells expressing the same k-type MHC protein, but they did not lyse infected cells from mice expressing d-type class I MHC proteins (Figure Q242). Similarly, cytotoxic T cells from d-type mice lysed infected d-type cells, but not infected k-type cells. LCMV can kill both k-type and d-type mice. A. If homozygous d-type mice were bred to homozygous k-type mice to generate d-type/k-type heterozygous progeny, would you expect that cytotoxic T cells from these heterozygotes, when infected with LCMV, to be able to lyse infected d-type cells? How about infected k-type cells? Explain your answers. B. Oddly enough, LCMV infection does not kill mice that lack a thymussuch as nude mice, so called because they also lack hair. If a thymus is transplanted back into a nude mouse, it will die when infected with LCMV. Suppose that a d-type/k-type heterozygous nude mouse was given a thymus from an d-type donor. Would you expect its cytotoxic T cells to be able to lyse infected d-type cells? How about infected k-type cells? Explain your answers.

Before exposure to a foreign antigen, T cells with receptors specific for the antigen are a tiny fraction of the T cellson the order of 1 in 105 or 1 in 106 T cells. After exposure to the antigen, only a small number of dendritic cells typically display the antigen on their surface. How long does it take for such antigen-presenting dendritic cells to interact with the antigen-specific T cells, which is the key first step in T cell activation and clonal expansion? The dynamics of the search process were examined by labeling dendritic cells red and T cells green, so that contacts in an intact lymph node could be scored visually using two-photon fluorescence microscopy (Figure Q243A). The frequency of contacts between dendritic cells and T cells from such experiments is given in Figure 243B. Assuming that 100 dendritic cells present the specific antigen, how long would it take them to scan 105 T cells? How long for 106 T cells?

At first glance, it would seem a dangerous strategy for the thymus to actively promote the survival, maturation, and emigration of developing T cells that bind weakly to self peptides bound to self MHC molecules. Would it not be safer to get rid of these T cells, along with those that bind strongly to such self-peptideMHC complexes, as this would seem a more secure way to avoid autoimmune reactions?

CD4 proteins on helper and regulatory T cells serve as co-receptors that bind to invariant parts of class II MHC proteins. CD4 is thought to increase the adhesion between T cells and antigen-presenting cells (APCs) that are initially connected only weakly by the T cell receptor bound to its specific peptideMHC complex. To test this possibility, you label cell-surface MHC molecules with a fluorescently labeled peptide so that you can detect individual peptideMHC complexes at the interface between the APCs and the T cells in a culture dish. To detect T cell responsesthe sign of a productive contactyou load them with a Ca2+ indicator dye, as cytosolic Ca2+ increases when lymphocytes are active. You now count the peptide MHC complexes at a large number of interfaces (immunological synapses) and measure the resulting uptake of Ca2+ in the adherent T cells (Figure Q244, red circles). When you repeat the experiment in the presence of blocking antibodies against CD4, you get a different result (blue circles). Do these results support or refute the notion that CD4 augments T cell receptor binding? Explain your answer.