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Publication : The biological activity of natural and mutant pTalpha alleles.

First Author  Gibbons D Year  2001
Journal  J Exp Med Volume  194
Issue  5 Pages  695-703
PubMed ID  11535637 Mgi Jnum  J:71362
Mgi Id  MGI:2149875 Doi  10.1084/jem.194.5.695
Citation  Gibbons D, et al. (2001) The biological activity of natural and mutant pTalpha alleles. J Exp Med 194(5):695-703
abstractText  beta selection is a major checkpoint in early thymocyte differentiation, mediated by successful expression of the pre-T cell receptor (TCR) comprising the TCRbeta chain, CD3 proteins, and a surrogate TCRalpha chain, pTalpha. The mechanism of action of the pre-TCR is unresolved. In humans and mice, the pTalpha gene encodes two RNAs, pTalpha(a), and a substantially truncated form, pTalpha(b). This study shows that both are biologically active in their capacity to rescue multiple thymocyte defects in pTalpha(-/-) mice. Further active alleles of pTalpha include one that lacks both the major ectodomain and much of the long cytoplasmic tail (which is unique among antigen receptor chains), and another in which the cytoplasmic tail is substituted with the short tail of TCR Calpha. Thus, very little of the pTalpha chain is required for function. These data support a hypothesis that the primary role of pTalpha is to stabilize the pre-TCR, and that much of the conserved structure of pTalpha probably plays a critical regulatory role.
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