From the peripheral blood of the melanoma patient (AV), we derived cytolytic T lymphocyte (CTL) clones that lysed the autologous tumor line SK-MEL-29, but not autologous EBV-B cells, K562, and other tumor targets. By immunoselection experiments it was shown that the CTL clones recognized at least three different antigens on the autologous tumor cells. We demonstrate here that these melanoma antigens are presented to the CTL in association with HLA-A2. First, HLA-A2-reactive pregnancy sera as well as an mAb against HLA-A2 inhibited the CTL lysis. Second, immunoselected melanoma subclones that were resistant to lysis by CTL clones against the three antigens described were found to lack expression of HLA-A2. By sensitizing the patient's lymphocytes against an HLA-A2- melanoma clone, we established a new series of CTL clones recognizing autologous AV melanoma cells. However, efficient lysis was only seen when target cells were pretreated with IFN-gamma. The lytic activity of these CTL was selectively inhibited by an mAb against a common HLA-B determinant. These results indicate that in addition to HLA-A2, other class I antigens are involved in the recognition of AV melanoma cells by autologous CTL.

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Since the most recent outbreak, the Ebola virus (EBOV) epidemic remains one of the world’s public health and safety concerns. EBOV is a negative-sense RNA virus that can infect humans and non-human primates, and causes hemorrhagic fever. It has been proposed that the T-cell immunoglobulin and mucin domain (TIM) family proteins act as cell surface receptors for EBOV, and that the interaction between TIM and phosphatidylserine (PS) on the surface of EBOV mediates the EBOV–host cell attachment. Despite these initial findings, the biophysical properties of the TIM-EBOV interaction, such as the mechanical strength of the TIM-PS bond that allows the virus-cell interaction to resist external mechanical perturbations, have not yet been characterized. This study utilizes single-molecule force spectroscopy to quantify the specific interaction forces between TIM-1 or TIM-4 and the following binding partners: PS, EBOV virus-like particle, and EBOV glycoprotein/vesicular stomatitis virus pseudovirion. Depending on the loading rates, the unbinding forces between TIM and ligands ranged from 40 to 100 pN, suggesting that TIM-EBOV interactions are mechanically comparable to previously reported adhesion molecule–ligand interactions. The TIM-4–PS interaction is more resistant to mechanical force than the TIM-1–PS interaction. We have developed a simple model for virus–host cell interaction that is driven by its adhesion to cell surface receptors and resisted by membrane bending (or tension). Our model identifies critical dimensionless parameters representing the ratio of deformation and adhesion energies, showing how single-molecule adhesion measurements relate quantitatively to the mechanics of virus adhesion to the cell.

In der kontinuierlichen Polyacrylamid-Elektrophorese wurden 132 Seren von Patienten mit entzündlichen und malignen Prozessen der Lunge untersucht. Die quantitative Auswertung aller aufgetrennten Proteinfräktionen ergab beim Vergleich mit Normalseren eine auffällige Vermehrung der Haptoglobin-Polymerenpeaks des Hp 2-2-und Hp 2-l-Typs sowie des Haptoglobin-Monomerpeaks beim Hp l-l-Typ. Die Haptoglobinspiegel der Seren bei entzündlichen Lungenerkrankungen verschiedenster Art waren signifikant niedriger als bei Bronchialneoplasmen und signifikant erhöht gegenüber Normalseren. Pherogramme von Carcinomen im Frühstadium zeigten bereits charakteristisch hohe Haptoglobinwerte. Die Lungenerkrankungen verursachten daneben signifikant niedrigere Serum-Transferrinwerte. Eindeutige Veränderungen anderer Serumproteine wurden nicht festgestellt. Die quantitative Bestimmung des Transferrins und der Haptoglobine mittels der Elektrophorese ermöglicht damit differentialdiagnostische Aussagen bei Lungenprozessen und läßt sich auch zur Frühdiagnose des Lungencarcinoms einsetzen. Continuous polyacrylamide electrophoresis IL The diagnosis of malignant and inflammatory lung conditions132 Sera from patients with inflammatory and malignant lung conditions were investigated by continuous polyacrylamide electrophoresis. All the separated protein fractions were evaluated quantitatively and compared with those of normal sera. There was a marked increase in the Hp 2-2-and Hp 2-1-type haptoglobin polymer peaks and in the Hp 1-1-type haptoglobin monomer peak. The haptoglobin concentrations in the sera during various inflammatory lung conditions were significantly lower than those in patients with bronchial neoplasms, but they were significantly higher compared to normal sera. Pherograms of early stage carcinomas showed a characteristically high haptoglobin value. Moreover, the lung diseases caused -a significantly lower serum transferrin value. No marked changes were detected in the other serum proteins. On the basis of the present findings, the quantitative electrophoretic determination of transferrin and haptoglobin may help in the differential diagnosis of lung conditions and may be used for the early diagnosis of carcinoma of the lung.In der Differentialdiagnose von malignen und entzündlichen Prozessen der Lunge haben die herkömm-lichen Elektrophoreseverfahren wie die Papier-, die Celluloseacetat-oder die Stärkegelelektrophorese keine Bedeutung erlangt. Die Gründe sind in der mangelhaften Fraktionierung der Serumproben zu suchen. Weitaus bessere Auftrennungen von Serumproteinen werden mit neuen Trägermaterialien erreicht. Die Elektrophorese in Polyacrylamid ist in der biochemischen Forschung als eine der zur Zeit besten Trennmethoden für Proteine weitverbreitet. In Gebrauch ist hauptsächlich die aufwendigere diskontinuierliche (Disk-)Elektrophorese nach ORNSTEIN und DAVIS. Wir haben die einfachere kontinuierliche Polyacrylamid-Elektrophorese methodisch verbessert und standardisiert (1). Die erhaltenen Trennungen von Serumproteinen sind denen...