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V A Wallace

Publications and source records attributed to V A Wallace.

28 records · Page 2Linked to original sources
PubMed1993

CD4, CD8 and tyrosine kinases in thymic selection.

Analysis of T-cell development in transgenic and gene-deficient mice suggests that the co-receptor function of CD8 is essential for positive selection. Recent data also demonstrate that the requirement for CD4 and CD8 in negative selection of T cells is not absolute and may be regulated by T-cell receptor affinity for the deleting ligand, an interpretation consistent with the affinity model of thymic selection. In addition to its association with CD4 and CD8, it appears that p56lck is also important during the early stages of thymic development.

Animals↗
PubMed1992

CD45RA and CD45RBhigh expression induced by thymic selection events.

CD45 is a protein tyrosine phosphatase involved in T and B cell signaling. While peripheral T cells switch CD45 isoforms upon activation, events leading to exon switching during T cell development in the thymus have not been determined. The expression of high molecular weight isoforms of CD45 was examined on thymocytes from nontransgenic and T cell receptor (TCR) transgenic mice. All thymocytes from nontransgenic mice were CD45RB+ as assessed by staining with MB23G2, an anti-CD45RB-specific monoclonal antibody. Interestingly, there was a small population (1-3%) of thymocytes that displayed a higher intensity of staining with MB23G2, CD45RBhigh. CD45RBhigh thymocytes were found in all subsets defined by CD4 and CD8 expression and were also present within the TCR-alpha/beta high population. To analyze whether or not CD45 expression correlated with thymic selection events, expression of CD45RBhigh and a second isoform, CD45RA, was examined on thymocytes from H-Y and 2C TCR transgenic mice and found to correlate with positive and negative selection events but did not occur in nonselecting backgrounds. CD45RA and CD45RBhigh upregulation was also not observed in transgenic mice backcrossed into CD8-deficient mice, a scenario in which there is no positive selection of transgene-expressing thymocytes. These data suggest that modulation of CD45 isoform expression may be involved in thymic selection events.

Animals↗
PubMed1992

CD4 expression is differentially required for deletion of MLS-1a-reactive T cells.

Clonal deletion of thymocytes expressing potentially self-reactive T cell receptors (TCRs) occurs during thymocyte ontogeny. Mice deficient for CD4 expression provide a unique model system to study the contribution of the CD4 molecule in negative selection of T cells reactive against the major histocompatibility complex class II-associated retroviral self-superantigen, Mls-1a. In the presence of Mls-1a determinants, mature CD8+ T cells expressing V beta 6, 8.1, and 9 were deleted in CD4-deficient mice, thus demonstrating that TCR affinity for Mls-1a is sufficient for deletion and that a signal through CD4 was not required. However, in instances where the TCR affinity for Mls-1a is low, as in the case of V beta 7+ T cells, CD4 expression was required for clonal deletion. These results demonstrate that for Mls-1a-mediated clonal deletion of T cells, the requirement for the accessory or coreceptor function of CD4 depends on the affinity of the TCR.

Animals↗
PubMed1991

Involvement of both T cell receptor V alpha and V beta variable region domains and alpha chain junctional region in viral antigen recognition.

We have studied the lymphocytic choriomeningitis virus (LCMV)-specific cytotoxic T cell response in transgenic mice expressing either the T cell receptor (TcR) alpha (V alpha 2/J alpha TA31) or the corresponding TcR beta (V beta 8.1/D beta/J beta 2.4) chain originally isolated from the LCMV glycoprotein specific (residues 32-42), H-2Db-restricted T cell clone P14. The expression of single transgenic TcR chains did not influence the corresponding endogenous TcR V gene usage in unstimulated T cells indicating that one particular TcR alpha or beta chain can randomly pair with different V beta or V alpha chains without any obvious bias. However, upon infection with LCMV, reactive cytotoxic T lymphocytes (CTL) from P14 beta-transgenic mice were predominantly V alpha 2+ whereas CTL from P14 alpha-transgenic mice preferentially expressed V beta 8.1 and unexpectedly also V beta 8.3 (but not V beta 8.2). Correspondingly, the LCMV-specific CTL response in both alpha and beta TcR-transgenic mice was strongly biased to the original P14 T cell epitope (LCMV glycoprotein residues 32-42). Sequence analysis of a large panel of LCMV-reactive "half-transgenic" TcR from P14 single receptor chain-transgenic mice revealed a highly conserved VJ alpha and a more diverse VDJ beta junctional region. This report demonstrates that the antigen specificity of the studied TcR depends on the specific combination of both TcR alpha and beta chains which implies that amino acids located in the TcR V alpha and V beta segments as well as in the junctional region are involved in binding of the viral antigenic fragment.

Amino Acid Sequence↗
PubMed1991

Biology of murine gamma delta T cells.

Murine lymphocytes express either a T-cell receptor alpha beta or a gamma delta heterodimer. The function of alpha beta cells are well characterized, while gamma delta cells remain an enigmatic population. In the mouse, gamma delta cells appear in significant proportions in the epithelia of various nonlymphoid tissues such as the skin, intestine, tongue, lung, and reproductive organs. While gamma delta T-cell subsets with distinct antigen receptor repertoires are associated with certain organs, diversified populations of gamma delta cells showing heterogeneous TCR phenotypes, as a result of junctional region diversification and usage of different V chains, can be found in the lymphoid organs and in the intestinal epithelia. Recent evidence has shown that gamma delta cells might recognize heat shock proteins, possibly in association with classical and nonpolymorphic MHC molecules. Together with their tissue distribution, gamma delta cells may represent the first line of defense of the immune system. gamma delta Cells are the first T cells to colonize the thymus. Intriguingly, there is more evidence to support the hypothesis that they might also affect the development of alpha beta cells and other hematopoietic stem cells.

Animals↗
PubMed1990

Specific deletion of the J-C delta locus in murine alpha/beta T cell clones and studies using transgenic mice.

A deletion event in the T cell receptor (TcR) delta locus has been characterized in a panel of mouse alpha/beta cytotoxic T lymphocyte (CTL) clones. Data presented here shows that J delta 1, J delta 2 and C delta are absent from functional CTL clones while a germ-line D delta 1 fragment is retained, thus suggesting a specific deletion of this region. We have investigated the possible significance of the J-C delta deletion by generating T cell lines from TcR alpha/beta transgenic mice. Unlike control T cell lines which included a T cell line derived from a beta transgenic mouse, the lines expressing the transgenic alpha/beta heterodimer have not deleted the C delta region. This strongly suggests that the J-C delta deletion event is not responsible for directing T cells to the alpha/beta lineage, but rather is involved in the rearrangement or transcriptional activity of the alpha locus. In addition, to ensure that the alpha/beta transgene does not have any inhibitory affects on the rearrangement of the delta loci in general, the gamma/delta expressing dendritic epithelial T cell (DETC) population was examined in TcR alpha/beta transgenic mice and alterations in this T cell subset were not found. This finding that normal gamma/delta DETC cells are present in alpha/beta transgenic mice, together with the data showing that the D delta 1 region remains in an unrearranged germ-line configuration in functional alpha/beta CTL, suggests that commitment to the alpha/beta or gamma/delta lineage is predetermined at a particular stage in early T cell ontogeny.

Animals↗
PubMed1990

Expression of CD4 can confer major histocompatibility complex class II-associated superantigen reactivity upon a T cell receptor derived from a CD8-dependent cytotoxic T lymphocyte clone.

It has been shown that reactivity against major histocompatibility complex (MHC) class II-associated Mlsa determinants is mainly mediated by CD4+ V beta 6+ T cells. 3F9 is a CD8+ CTL clone which is specific for the alloantigen H-2Db. While 3F9 is V beta 6+, it is not Mlsa reactive, presumably because it does not express CD4. 3F9 utilizes the same T cell receptor (TcR) V alpha V beta combination as LB2, a CD4+ T helper clone specific for chicken red blood cells (cRBC)/I-Ab and yet differs from LB2 in the junctional sequences in both TcR chains. CD4+ CD8- and CD4-CD8- hybridomas expressing the 3F9 TcR were tested for reactivity against Mlsa and cRBC/I-Ab. Only the CD4+CD8- hybridomas were Mlsa reactive, and antibody inhibition studies revealed that this reactivity was both CD4 and MHC class II dependent. Therefore the expression of the CD4 molecule can make an MHC class I-restricted TcR Mlsa reactive. Neither type of hybridoma reacted against cRBC, thus the main difference in the antigen reactivity between 3F9 and LB2 lies in the TcR junctional regions.

Animals↗