Control of genotypic allelic inclusion through TCR surface expression.
نویسندگان
چکیده
To gain insight into the molecular causes and functional consequences of allelic inclusion of TCR alpha-chains, we develop a computational model for thymocyte selection in which the signal that determines cell fate depends on surface expression. Analysis of receptor pairs on selected dual TCR cells reveals that allelic inclusion permits both autoreactive TCR and receptors not in the single TCR cell repertoire to be selected. However, in comparison with earlier theoretical studies, relatively few dual TCR cells display receptors with high avidity for thymic ligands because their alpha-chains compete aggressively for the beta-chain, which hinders rescue from clonal deletion. This feature of the model makes clear that allelic inclusion does not in itself compromise central tolerance. A specific experiment based on modulation of TCR surface expression levels is proposed to test the model.
منابع مشابه
Assembly of Productive T Cell Receptor δ Variable Region Genes Exhibits Allelic Inclusion
The generation of a productive "in-frame" T cell receptor beta (TCR beta), immunoglobulin (Ig) heavy (H) or Ig light (L) chain variable region gene can result in the cessation of rearrangement of the alternate allele, a process referred to as allelic exclusion. This process ensures that most alphabeta T cells express a single TCR beta chain and most B cells express single IgH and IgL chains. As...
متن کاملPosttranslational regulation of TCR Valpha allelic exclusion during T cell differentiation.
We have previously shown that phenotypic allelic exclusion of TCR alpha-chain is functional only in mature thymocytes. A significant proportion of immature thymocytes (TCRlow) express more than one cell surface alpha-chain, but mature thymocytes (TCRhigh) show phenotypic allelic exclusion and express only a single alpha-chain. We have analyzed thymocytes for both surface and intracellular alpha...
متن کاملAllelic Exclusion in pTα-deficient Mice: No Evidence for Cell Surface Expression of Two T Cell Receptor (TCR)-β Chains, but Less Efficient Inhibition of Endogeneous Vβ→ (D)Jβ Rearrangements in the Presence of a Functional TCR-β Transgene
Although individual T lymphocytes have the potential to generate two distinct T cell receptor (TCR)-beta chains, they usually express only one allele, a phenomenon termed allelic exclusion. Expression of a functional TCR-beta chain during early T cell development leads to the formation of a pre-T cell receptor (pre-TCR) complex and, at the same developmental stage, arrest of further TCR-beta re...
متن کاملExclusion and inclusion of TCR alpha proteins during T cell development in TCR-transgenic and normal mice.
Allelic exclusion of immune receptor genes (and molecules) is incompletely understood. With regard to TCRalphabeta lineage T cells, exclusion at the tcr-b, but not tcr-a, locus seems to be strictly controlled at the locus rearrangement level. Consequently, while nearly all developing TCRalphabeta thymocytes express a single TCRbeta protein, many thymocytes rearrange and express two different TC...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 175 10 شماره
صفحات -
تاریخ انتشار 2005