Academic Journal
Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion
| العنوان: | Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion |
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| المؤلفون: | Zernich, Danielle, Purcell, Anthony W., Macdonald, Whitney A., Kjer-Nielsen, Lars, Ely, Lauren K., Laham, Nihay, Crockford, Tanya, Mifsud, Nicole A., Bharadwaj, Mandvi, Chang, Linus, Tait, Brian D., Holdsworth, Rhonda, Brooks, Andrew G., Bottomley, Stephen P., Beddoe, Travis, Peh, Chen Au, Rossjohn, Jamie, McCluskey, James |
| المصدر: | The Journal of Experimental Medicine ; volume 200, issue 1, page 13-24 ; ISSN 1540-9538 0022-1007 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2004 |
| الوصف: | HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1084/jem.20031680 |
| الاتاحة: | http://dx.doi.org/10.1084/jem.20031680 https://rupress.org/jem/article-pdf/200/1/13/1714526/jem200113.pdf |
| رقم الانضمام: | edsbas.1754D85 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1084/jem.20031680 |
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