Developmentally regulated expression of T cell receptor beta chain variable domains in immature thymocytes.

Abstract

The process by which developing T lymphocytes are selected within the thymus is basic to the acquisition of T cell tolerance and MHC restriction of antigen recognition. As repertoire determination likely occurs based upon the specificity of TCR molecules (1), identification of the stage at which surface TCR first appears on immature thymocytes is fundamental to studies of the selection mechanism.The genes encoding the disulfide-linked a-and ,B-chain subunits of the TCR resemble Ig genes in their structure, requirement for DNA rearrangement before expression, and developmental regulation (2). Thus, immature thymocytes, lacking expression of the differentiation antigens CD4 (L3T4 in mouse) and CD8 (Lyt-2), express high levels of a-chain transcripts but very low levels of a-chain transcripts, and no surface TCR protein has been observed on these cells (3-6). However, CD4-,8-thymocytes contain cells at various stages of differentiation (7-9). We show here that a minor (10%) subset of CD4-,8-thymocytes transcribes abundant amounts of a-chain and ,8-chain mRNA and expresses low levels of surface TCR protein . Interestingly, these early T cells show a preferential use of a particular ,3-chain variable segment gene family (V,6s) at both the RNA and protein levels .

NKT cells: In the beginning…

“…By pure serendipity these mAb were both directed against the Vb8 domain that is dramatically over-represented among iNKT cells. Thus it rapidly became clear that the DN thymocyte subset had a TCR repertoire that was heavily biased towards Vb8 [1][2][3].…”

“…Based on the dogma that DN thymocytes were immature, we speculated that the Vb8-biased subset might arise from preferential usage of certain Vb domains early in development [1] …”

“…In the summer of 1987 two groups independently reported the identification of a mysterious subset of CD4 -CD8 -(double-negative, DN) thymocytes that overexpress the TCR Vb8 gene segment [1,2]. A third report followed shortly thereafter [3].…”

“…By pure serendipity these mAb were both directed against the Vb8 domain that is dramatically over-represented among iNKT cells. Thus it rapidly became clear that the DN thymocyte subset had a TCR repertoire that was heavily biased towards Vb8 [1][2][3].With hindsight it is interesting to note that this first glimpse of iNKT cells was interpreted incorrectly by both groups that made the initial discovery. Based on the dogma that DN thymocytes were immature, we speculated that the Vb8-biased subset might arise from preferential usage of certain Vb domains early in development [1] …”

“…Thus it rapidly became clear that the DN thymocyte subset had a TCR repertoire that was heavily biased towards Vb8 [1][2][3].…”