A malaria merozoite surface protein (MSP1)-structure, processing and function.

Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is one of the most studied of all malaria proteins. The protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. Studies on Plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large precursor molecule. Recent studies have identified some of these cleavage sites. During invasion of the new red cell most of the MSP1 molecule is shed from the parasite surface except for a small C-terminal fragment which can be detected in ring stages. Analysis of the structure of this fragment suggests that it contains two growth factor-like domains that may have a functional role.

Altered antigen receptor signaling in anergic T cells from self-tolerant T-cell receptor beta-chain transgenic mice.

T-cell tolerance to the minor lymphocyte-stimulating antigen Mls-1a in a T-cell receptor (TcR) V beta 8.1 transgenic line of mice is maintained by both clonal deletion and clonal anergy. Approximately 20-50% of peripheral CD4+ (but not CD8+) T cells isolated from these mice are anergic and fail to proliferate following TcR ligation. We have examined key events in T-cell signaling in peripheral T cells isolated from these mice. In this report, we show that the anergic CD4+ T cells did not mobilize calcium or express receptors for interleukin 2 (IL-2) following TcR ligation. However, the cells retained viability and functional potential because stimulation with phorbol 12-myristate 13-acetate and ionomycin bypassed the block in receptor-mediated signaling and induced IL-2 receptor expression and proliferation of the anergic cells.

The role of the T cell receptor in positive and negative selection of developing T cells.

Although many combinations of alpha beta T cell receptors are available to the T cells in any given organism, far fewer are actually used by mature T cells. The combinations used are limited by two selective processes, positive selection of T cells bearing receptors that will be useful to the host, and clonal elimination or inactivation of T cells bearing receptors that will be damaging to the host. The ways in which these two apparently contradictory processes occur, and the hypotheses that have been suggested to reconcile them, are discussed.

Two better cell lines for making hybridomas expressing specific T cell receptors.

Two variants of the AKR thymoma BW5147 have been isolated which can no longer express functional TCR alpha- and beta-chains. By generating hybridomas with these variant fusion lines, TCR of any normal T lymphocyte, including TCR-gamma/delta, can be studied at a clonal level, without interference of the BW5147-derived receptor chains. In this study one of the variants has been useful in identifying the reactivity to allogeneic MHC Ag of BW5147 itself.

Influence of the major histocompatibility complex on positive thymic selection of V beta 17a+ T cells.

A monoclonal antibody was used to show directly positive thymic selection of the T cell repertoire in mouse strains expressing the 17a beta-chain variable domain (V beta 17a) of the T cell receptor. In the absence of the potent tolerizing class II major histocompatibility complex (MHC) molecule, I-E, peripheral expression of V beta 17a+ T cell receptors varied with the MHC haplotype of the mouse strain. In the most extreme case, H-2q mice expressed high peripheral levels of CD4+ V beta 17a+ T cells (14 to 19 percent), whereas H-2b mice expressed low levels (3 to 4 percent). Analysis of (b x q)F1 mice and chimeric mice showed that these differences were determined by positive thymic selection and implicated the thymic epithelium as the controlling cell type.

The structure of V alpha and J alpha segments in the mouse.

Antigen receptors on most T-cells are heterodimeric glycoproteins, comprised of an alpha chain and a beta chain. These chains are encoded by discontiguous variable (V), diversity (D) and joining (J) gene segments that rearrange to produce a contiguous and functional alpha or beta chain gene. To investigate the size and diversity of the germline repertoire of alpha-chain gene segments, we have characterized and sequenced 20 alpha chain cDNAs. Among these cDNA clones, we have found 4 J alpha and 4 V alpha sequences that have not yet been described. The relationship of these "new" gene segments to those already characterized is discussed.

Ventricular arrhythmias and mitral valve prolapse in childhood.

Although ventricular arrhythmias are well described in adults with mitral valve prolapse, this association remains controversial in children. To assess the incidence of ventricular premature complexes (VPCs), 103 consecutive children with mitral valve (MV) prolapse confirmed by echocardiography were evaluated prospectively by treadmill exercise and ambulatory ECG. A group of 50 normal children with clinical, ECG, or echocardiographic evidence of heart disease who had undergone treadmill exercise and ambulatory ECG served as controls. In the group with MV prolapse, 16 patients had VPCs with treadmill exercise and 39 had VPCs on ambulatory ECG. High-grade ventricular ectopy (multiform VPCs, couplets, or ventricular tachycardia) was recorded in four patients with MV prolapse during treadmill exercise and in eight during ambulatory ECG. In contrast, no control patient had a single VPC in response to treadmill exercise and only four control patients had rare uniform VPCs on ambulatory ECG. Neither physical examination findings, standard ECG results, nor symptoms could be correlated with VPCs in the patients with MV prolapse. Although the prognostic implications of these findings are uncertain, this study demonstrates that potentially serious ventricular arrhythmias are frequently observed in children with MV prolapse.