Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors

BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS tumors of infancy and early childhood. Hallmark is the surprisingly simple genome with inactivating mutations or deletions in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T cells. However, it is unclear which epitopes T cells might recognize on AT/RT cells. METHODS: Here, we report a comprehensive mass spectrometry (MS)-based analysis of naturally presented human leukocyte antigen (HLA) class I and class II ligands on 23 AT/RTs. MS data were validated by matching with a human proteome dataset and exclusion of peptides that are part of the human benignome. Cryptic peptide ligands were identified using Peptide-PRISM. RESULTS: Comparative HLA ligandome analysis of the HLA ligandome revealed 55 class I and 139 class II tumor-exclusive peptides. No peptide originated from the SMARCB1 region. In addition, 61 HLA class I tumor-exclusive peptide sequences derived from non-canonically translated proteins. Combination of peptides from natural and cryptic class I and class II origin gave optimal representation of tumor cell compartments. Substantial overlap existed with the cryptic immunopeptidome of glioblastomas, but no concordance was found with extracranial tumors. More than 80% of AT/RT exclusive peptides were able to successfully prime CD8(+) T cells, whereas naturally occurring memory responses in AT/RT patients could only be detected for class II epitopes. Interestingly, >50% of AT/RT exclusive class II ligands were also recognized by T cells from glioblastoma patients but not from healthy donors. CONCLUSIONS: These findings highlight that AT/RTs, potentially paradigmatic for other pediatric tumors with a low mutational load, present a variety of highly immunogenic HLA class I and class II peptides from canonical as well as non-canonical protein sources. Inclusion of such cryptic peptides into therapeutic vaccines would enable an optimized mapping of the tumor cell surface, thereby reducing the likelihood of immune evasion

Asynchrones optisches Abtasten : Weiterentwicklung und Anwendung

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Laser-based ultrasonics for metrology applications

Die optische Erzeugung und Detektion von Ultraschall durch Absorption ultrakurzer Laserpulse ermöglicht die Messung charakteristischer Materialparameter. Mit einem Hochgeschwindigkeits-Anrege-Abfrage-System, basierend auf zwei zueinander synchronisierten Titan-Saphir-Lasern, können Schichtdicken von Vielschichtsystemen mit kHz-Abtastraten und einer Tiefenauflösung im sub-nm-Bereich bestimmt werden. Durch eine flexible Glasfaserkopplung eignet sich das Messsystem für große und komplexe Flächen sowie für schwer zugängliche Bereiche

Consistent characterization of semiconductor saturable absorber mirrors with singe-pulse and pump-probe spectroscopy

We study the comparability of the two most important measurement methods used for the characterization of semiconductor saturable absorber mirrors (SESAMs). For both methods, single-pulse spectroscopy (SPS) and pump-probe spectroscopy (PPS), we analyze in detail the time-dependent saturation dynamics inside a SESAM. Based on this analysis, we find that fluence-dependent PPS at complete spatial overlap and zero time delay is equivalent to SPS. We confirm our findings experimentally by comparing data from SPS and PPS of two samples. We show how to interpret this data consistently and we give explanations for possible deviations

Terahertz emission based on large-area photoconductive emitters illuminated via beam interference

The use of beam interference in combination with a large-area photoconductive emitter for the generation of pulsed terahertz (THz) radiation is presented. An interference pattern with a period twice that of the THz emitter is generated with a transmission phase grating, placed directly in front of the photoconductive emitter. This way, efficient THz generation is achieved with a single metallisation layer and a single lithography step in the fabrication technology of the THz emitter

Fiber-coupled high-speed asynchronous optical sampling with sub-50 fs time resolution

We present a fiber-coupled pump-probe system with a sub-50 fs time resolution and a nanosecond time window, based on high-speed asynchronous optical sampling. By use of a transmission grism pulse compressor, we achieve pump pulses with a pulse duration of 42 fs, an average power of 300 mW and a peak power exceeding 5 kW at a pulse repetition rate of 1 GHz after 6 m of optical fiber. With this system we demonstrate thickness mapping of soft X-ray mirrors at a sub-nm thickness resolution on a cm2 scan area. In addition, terahertz field generation with resolved spectral components of up to 3.5 THz at a GHz frequency resolution is demonstrated

High-speed asynchronous optical sampling based on GHz Yb:KYW oscillators

A low-cost scheme of high-speed asynchronous optical sampling based on Yb:KYW oscillators is reported. Two GHz diode-pumped oscillators with a slight pulse repetition rate offset serve as pump and probe source, respectively. The temporal resolution of this system is limited to 500 fs mainly by the pulse duration of the oscillators and also by relative timing jitter between the oscillators. A near-shot-noise noise floor around 10^−6 (∆R/R) is obtained within a data acquisition time of a few seconds. The performance of the system is demonstrated by measurements of coherent acoustic phonons in a semiconductor sample that resembles a semiconductor saturable absorber mirror or an optically pumped semiconductor chip

Two-colour high-speed asynchronous optical sampling based on offset-stabilized Yb:KYW and Ti:sapphire oscillators

We present a high-speed asynchronous optical sampling system, based on two different Kerr-lens mode-locked lasers with a GHz repetition rate: An Yb:KYW oscillator and a Ti:sapphire oscillator are synchronized in a master-slave configuration at a repetition rate offset of a few kHz. This system enables two-colour pump-probe measurements with resulting noise floors below 10-6 at a data aquisition time of 5 seconds. The measured temporal resolution within the 1 ns time window is below 350 fs, including a timing jitter of less than 50 fs. The system is applied to investigate zone-folded coherent acoustic phonons in two different semiconductor superlattices in transmission geometry at a probe wavelength far below the bandgap of the superlattice constituents. The lifetime of the phonon modes with a zero wave vector and frequencies in the range from 100 GHz to 500 GHz are measured at room temperature and compared with previous wor