A personal retrospective on the mechanisms of antigen processing
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My intention here is to describe the history of the molecular aspects of the antigen processing field from a personal perspective, beginning with the early identification of the species that we now know as MHC class I and MHC class II molecules, to the recognition that their stable surface expression and detection by T cells depends on peptide association, and to the unraveling of the biochemical and cell biological mechanisms that regulate peptide binding. One goal is to highlight the role that serendipity or, more colloquially, pure blind luck can play in advancing the research enterprise when it is combined with an appropriately receptive mind. This is not intended to be an overarching review, and because of my own work I focus primarily on studies of the human MHC. This means that I neglect the work of many other individuals who made advances in other species, particularly those who produced the many knockout mouse strains used to demonstrate the importance of the antigen processing machinery for initiating immune responses. I apologize in advance to colleagues around the globe whose contributions I deal with inadequately for these reasons, and to those whose foundational work is now firmly established in text books and therefore not cited. So many individuals have worked to advance the field that giving all of them the credit they deserve is almost impossible. I have attempted, while focusing on work from my own laboratory, to point out contemporaneous or sometimes earlier advances made by others. Much of the success of my own laboratory came because we simultaneously worked on both the MHC class I and class II systems and used the findings in one area to inform the other, but mainly it depended on the extraordinary group of students and fellows who have worked on these projects over the years. To those who worked in other areas who are not mentioned here, rest assured that I appreciate your efforts just as much.
KeywordsAntigens Molecular mechanisms MHC Serendipity Transplantation T cell responses
As stated at the outset, all progress would have been impossible without the contributions of the many students and postdoctoral fellows who have passed through my laboratory. Their hard work, creativity, dedication, and love of science made it all possible. My own mentors, the late Arnold Sanderson, Jack Strominger and, in particular, my role model at Duke, the late Bernard Amos, were all critical in their different ways to the development of my career. I also would like to express my appreciation to the dedicated technicians who made things work over the years and to the administrative staff who compensated for my organizational inadequacies. And of course, without 25 years of funding from the Howard Hughes Medical Institute and continuous funding since 1974 from the National Institute of Allergy and Infectious Diseases, my life would have taken quite a different turn. Finally, if this work seems far removed from an exercise in modesty, I would like all blame to be directed at Martin Flajnik for generously extending the invitation.
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