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Cytotoxic T cells (CTL) are an important arm of our immune defence against intracellular pathogens such as viruses, bacteria and parasites and can provide protection against the development of tumours. The picture to the right shows a swarm of CTL (coloured in white) attacking a tumour cell (coloured in orange). The outcome of this attack will be the destruction of the tumour cell. CTL recognise fragments of protein antigens (epitopes), derived from pathogens or tumours, bound to polymorphic receptor molecules encoded by the Major Histocompatibility Complex (class I) on the surface of infected cells.
The process of generating peptide fragments from pathogen proteins is known as antigen processing, and the formation of a complex, between these peptides and MHC class I molecules, which can be seen by circulating CTL is known as antigen presentation. It is the point where these two processes meet that has occupied me over the past ten years. Here, polypeptide fragments containing CTL epitopes are transported from the cytosol, where they are made, into the endoplasmic reticulum (ER) where MHC class I molecules are synthesised. This requires a specialised peptide transporter - the Transporter Associated with Antigen Processing or TAP. Once in the ER the polypeptide fragments can be trimmed to an optimal size for binding to newly synthesised MHC class I molecules by an aminopeptidase called ERAP. A process of molecular editing follows in order to ensure that only the most stable peptide:MHC complexes are released to the cell surface. Thus, intracellular peptide loading could be a major factor in determining the immunodominance of some peptide epitopes over others : watch the video made by Diego Arrosi and David Williams in Toronto for a great introduction to the subject (http://vimeo.com/27074960)
Our current research programme encompasses themes within the biology of antigen processing and presentation and immunity to tumours
研究兴趣
论文共 182 篇作者统计合作学者相似作者
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Nature Communications (2023)
Current opinion in immunology (2023): 102340-102340
Shivan Sivakumar,Ashwin Kumar Jainarayanan,Edward Arbe-Barnes, Máire Ní Leathlobhair,Piyush Kumar Sharma, Sanaz Amin,Lara Heij,Samarth Hegde,Assaf Magen,Felicia Anna Tucci,Bo Sun, Shihong Wu,
bioRxiv (Cold Spring Harbor Laboratory) (2023)
Immuno-Oncology Technology (2023): 100508-100508
Lion F K Uhl, Han Cai, Sophia L Oram,Jagdish N Mahale,Andrew J MacLean,Julie M Mazet, Theo Piccirilli,Alexander J He,Doreen Lau,Tim Elliott,Audrey Gerard
Nature communicationsno. 1 (2023): 6727-17
Lion F. K. Uhl, Han Cai, Sophia L. Oram,Jagdish N. Mahale,Andrew J. Maclean,Julie M. Mazet, Theo Piccirilli,Alexander J. He,Doreen Lau,Tim Elliott,Audrey Gerard
NATURE COMMUNICATIONSno. 1 (2023)
Molecular Immunology (2022): 27
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