By Frank J. Dixon
The Scripps study Institute, los angeles Jolla, CA. most up-to-date findings within the box of immunology. converted define structure.
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Additional resources for Advances in Immunology, Vol. 69
1993). , 1995). Thus, it appears that rearrangements at the TCRa locus continue on both alleles until a receptor is formed that can bind to thymic MHC molecules. , 1995). , 1997) (see Section 111,B). Therefore, functional TCRP chains relay a negative feedback to the second allele in the absence of TCRa, strongly suggesting a role of the pre-TCR in mediating allelic exclusion. If the pre-TCR were implicated in the arrest of further TCRP rearrangements, pTa-deficient mice should show signs of inefficient allelic exclusion, a hypothesis that has been tested in three experimental approaches.
The first pathway most likely represents a DNA repair response, requires the presence of p53, and results in the restoration of functional TCR rearrangements and formation of a conventional pre-TCR. This pathway is expected to dominate in irradiated SCID mice, as functional TCRP rearrangements should confer a significant advantage for cellular expansion, an assumption that is supported by the fact that about 90% of TCRP rearrangements found in thymi of irradiated SCID mice are productive. The second pathway is rearrangement independent and requires irradiation, not to induce a DNA damage response, but to mutationally inactivate p53 alleles in developmentally arrested thymocytes.
Mice are therefore most likely derived from these few T N CD25'TCRaP' thymocytes. According to this view, one would expect that mature T cells in pTn? mice do not carry more than one functional V( D)JP rearrangement, which would explain the absence of cells with two TCRP chains on the cell surface, despite the fact that allelic exclusion is compromised at the level of DNA rearrangements in pTadeficient mice. MOLECULAR AND CELLULAR EVENTS IN THYMOCYTE DEVELOPMENT 45 F. LIKELY COMPONENTS OF THE PRE-TCRSIGNAL TRANSDUCTION MACHINERY 1.
Advances in Immunology, Vol. 69 by Frank J. Dixon