Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding
- University of Oxford, United Kingdom
- University of Cambridge, United Kingdom
- University of Copenhagen, Denmark
- Pirbright Institute, United Kingdom
- The Royal Free Hospital, United Kingdom
Abstract
Highly polymorphic MHC molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and HIV infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation.
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Ethics
Animal experimentation: All procedures involving chickens were carried out at the University of Cambridge under Home Office project license PPL 80/2420 and with ethical approval of the Local Ethical Review Committee.
Human subjects: Anthony Nolan registrants signed written consent forms, with all procedures carried out under Human Tissue Act licensing number 22513 and with approval of the local Research Ethics committee (REC).
Reviewing Editor
- Arup K Chakraborty, Massachusetts Institute of Technology, United States
Version history
- Received: October 26, 2014
- Accepted: April 10, 2015
- Accepted Manuscript published: April 10, 2015 (version 1)
- Version of Record published: May 6, 2015 (version 2)
Copyright
© 2015, Chappell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding
eLife 4:e05345.
https://doi.org/10.7554/eLife.05345
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