The Molecular Basis of Thymocyte Positive Selection and CD4/CD8 Lineage Commitment

Author(s):  
Cynthia J. Guidos
1999 ◽  
Vol 64 (0) ◽  
pp. 51-60 ◽  
Author(s):  
S.L. NUTT ◽  
A.G. ROLINK ◽  
M. BUSSLINGER

2000 ◽  
Vol 165 (5) ◽  
pp. 2444-2450 ◽  
Author(s):  
M. Albert Basson ◽  
Timothy J. Wilson ◽  
Giuseppe A. Legname ◽  
Nitza Sarner ◽  
Peter D. Tomlinson ◽  
...  

2002 ◽  
Vol 168 (12) ◽  
pp. 6142-6151 ◽  
Author(s):  
Julie A. Lucas ◽  
Luana O. Atherly ◽  
Leslie J. Berg

2005 ◽  
Vol 201 (1) ◽  
pp. 149-158 ◽  
Author(s):  
Henry Kao ◽  
Paul M. Allen

The CD4 coreceptor works together with the T cell receptor (TCR) to deliver signals to the developing thymocyte, yet its specific contribution to positive selection and CD4 lineage commitment remains unclear. To resolve this, we used N3.L2 TCR transgenic, RAG-, and CD4-deficient mice, which are severely impaired in positive selection, and asked whether altered peptide ligands can replace CD4 function in vivo. Remarkably, in the presence of antagonist ligands that normally deleted CD4+ T cells in wild-type mice, we induced positive selection of functional CD4 lineage T cells in mice deficient in CD4. We show that the kinetic threshold for positive and negative selection was lowered in the absence of CD4, with no evident skewing toward the CD8 lineage with weaker ligands. These results suggest that CD4 is dispensable as long as the affinity threshold for positive selection is sustained, and strongly argue that CD4 does not deliver a unique instructional signal for lineage commitment.


2009 ◽  
Vol 5 (4) ◽  
pp. 513-516 ◽  
Author(s):  
David J. Moore ◽  
Damien C. T. Halliday ◽  
David M. Rowell ◽  
Anthony J. Robinson ◽  
J. Scott Keogh

Members of the Family Bufonidae, true toads, are famous for their endogenously synthesized cardioactive steroids that serve as defensive toxins. Evolution of resistance to these toxins is not understood. We sequenced a key region of the toxin's binding site in the Na + /K + ATPase for relevant taxa representing Hyloidea (including bufonids), Ranoidea and Archaeobatrachia and tested for positive selection in a phylogenetic context. Bufonidae were distinct from other Hyloidea at 4–6 of 12 sites and, with one exception, had a homologous amino acid sequence. Melanophryniscus stelzneri had a distinct sequence, consistent with other independent evidence for a differentiated toxin. Tests within Bufonidae detected positive selection within the binding region, providing, to our knowledge, the first evidence of this type for positive selection within Amphibia. There was no evidence for positive selection on Bufonidae or M. stelzneri lineages. Sequence change in Leptodactylus ocellatus , a leptodactylid predator of Bufonidae, provides a molecular basis for predator resistance possibly associated with gene duplication.


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