Definition of the Nature and Hapten Threshold of the β-Lactam Antigen Required for T Cell Activation In Vitro and in Patients

Xiaoli Meng; Zaid Al-Attar; Fiazia S. Yaseen; Rosalind Jenkins; Caroline Earnshaw; Paul Whitaker; Daniel Peckham; Neil S. French; Dean J. Naisbitt; B. Kevin Park

doi:10.4049/jimmunol.1700209

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Publication Date

Thu Jun 01 2017

Journal Name

The Journal Of Immunology

Volume

198

DOI

10.4049/jimmunol.1700209

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Definition of the Nature and Hapten Threshold of the β-Lactam Antigen Required for T Cell Activation In Vitro and in Patients

Xiaoli Meng

Zaid Al-Attar

Fiazia S. Yaseen

Rosalind Jenkins

Caroline Earnshaw

Paul Whitaker

Daniel Peckham

Neil S. French

Dean J. Naisbitt

B. Kevin Park

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Abstract<p>Covalent modification of protein by drugs may disrupt self-tolerance, leading to lymphocyte activation. Until now, determination of the threshold required for this process has not been possible. Therefore, we performed quantitative mass spectrometric analyses to define the epitopes formed in tolerant and hypersensitive patients taking the β-lactam antibiotic piperacillin and the threshold required for T cell activation. A hydrolyzed piperacillin hapten was detected on four lysine residues of human serum albumin (HSA) isolated from tolerant patients. The level of modified Lys541 ranged from 2.6 to 4.8%. Analysis of plasma from hypersensitive patients revealed the same pattern and levels of modification 1–10 d after the commencement of therapy. Piperacillin-responsive skin-homing CD4+ clones expressing an array of Vβ receptors were activated in a dose-, time-, and processing-dependent manner; analysis of incubation medium revealed that 2.6% of Lys541 in HSA was modified when T cells were activated. Piperacillin–HSA conjugates that had levels and epitopes identical to those detected in patients were shown to selectively stimulate additional CD4+ clones, which expressed a more restricted Vβ repertoire. To conclude, the levels of piperacillin–HSA modification that activated T cells are equivalent to the ones formed in hypersensitive and tolerant patients, which indicates that threshold levels of drug Ag are formed in all patients. Thus, the propensity to develop hypersensitivity is dependent on other factors, such as the presence of T cells within an individual’s repertoire that can be activated with the β-lactam hapten and/or an imbalance in immune regulation.</p>

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Проблемы преподавания русской литературы в иракской аудитории Problems of Teaching Russian Literature to Iraqi College Students

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русская литература

литературоведение

преподавание литературы

русский язык .

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Аннотация

в статье рассматриваются проблемы преподавания русской литературы в иракской аудитории.. Использование литературы в преподавании иностранного языка, как правило, имеет две цели. Первая-чисто лингвистическая .. Вторая цель, однако, ассоциируется больше с экстралингвистикой и представляет собой ознакомление студентов с различными аспектами русской жизни, культуры,

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The corrosion of carbon steel in single phase (water with 0.1N NaCl ) and two immiscible phases (kerosene-water) using turbulently agitated system is investigated. The experiments are carried out for Reynolds number (Re) range of 38000 to 95000 corresponding to rotational velocities from 600 to 1400 rpm using circular disk turbine agitator at 40 0C. In two-phase system test runs are carried out in aqueous phase (water) concentrations of 1 % vol., 5 % vol., 8% vol., and 16% vol. mixed with kerosene at various Re. The effect of Reynolds number (Re), percent of dispersed phase, dispersed drops diameter, and number of drops per unit volume on the corrosion rate is investigated and discussed. Test runs are carried out using two types of

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