Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells.

Abstract

T cell receptor (TCR) beta genes are rearranged prior to TCR alpha genes. A productively rearranged TCR beta gene suppresses further V beta gene rearrangement. Here we show that in beta TCR transgenic mice the TCR beta‐chain can be expressed on the surface of immature CD4–8– thymocytes, but not on mature T cells, in the absence of any other known TCR chain and proteins of the CD3 complex. Analysis by NEPHGE and SDS‐PAGE showed that at least some beta TCR exists on the surface as a large disulfide‐linked complex with unknown acidic molecules. The introduction of the beta TCR gene into scid mice resulted in the expression of the beta TCR on the cell surface of thymocytes and induced the expression of CD4 and CD8 co‐receptors as well as transcription of the alpha TCR locus.

Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of “ER-resident” molecular chaperones

“…Since surface expression of molecular chaperones is developmentally regulated, we considered that it might offer an explanation for expression on immature thymocytes of glycoproteins bearing incompletely processed N-linked carbohydrate side chains (25,48). In particular, we thought it possible that molecular chaperones continued to associate with glycoproteins even after escape from the ER, thereby blocking accessibility to processing enzymes during transit through the Golgi.…”

Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation.

“…Young, R. Phillips, F. Alt, unpubl.). It is possible to rationalize these findings based on considerations analogous to those considered previously for the relative ability of TCR~ or TCRe~ plus transgenes to rescue thymocyte and peripheral T-cell development in SCID versus RAG-deficient mice (Scott et al 1989;Kishi et al 1991;Mombaerts et al 1992;Shinkai et al 1992). Thus, it seems likely that HC/LC SCID mice still go through a stage in which rearrangements at either the HC or LC loci occur and which are lethal…”

Tyrosine phosphorylation of Blk and Fyn Src homology 2 domain-binding proteins occurs in response to antigen-receptor ligation in B cells and constitutively in pre-B cells.

“…Genetic experiments in which the membrane exons of the ,u heavy chain (9) or the A5 gene (10) were deleted by homologous recombination led to similar arrests of ontogeny at the late pre-B-cell stage, confirming the hypothesis that signal transduction through this pre-antigen receptor may play a critical role in late pre-B-cell survival. A similar selection mechanism has now been identified in the T-cell lineage, wherein cells that make an in-frame rearrangement at the T-cell-receptor j-chain locus receive a signal that permits further differentiation (11,12). In pre-T cells the ( chain of the T-cell receptor covalently associates with a 33-kDa glycoprotein that is presumed to represent the T-cell-lineage equivalent of the w chain (13).…”

“…Lysates from unstimulated (odd-numbered lanes) and anti-IgM-activated (even-numbered lanes) WEHI 231 cells were affinity-isolated by using the following GST fusion proteins and glutathione-Sepharose and analyzed after an in vitro kinase assay. Lanes: 1 and 2, GST; 3 and 4, GST-Btk-N terminus; 5 and 6, GST-Btk-SH3; 7 and 8, GST-Btk-SH2; 9 and 10, GST-Blk-N terminus; 11 In initial experiments we examined, by an in vitro kinase assay, proteins that bound to the N-terminal, SH2, and SH3 domains of Btk and the N-terminal and SH2 domains of Blk, using lysates from unstimulated and anti-IgM-stimulated WEHI 231 cells. As can be seen in Fig.…”