Discovered more than 50 years back by those grappling with the issue of graft rejection, the MHC provides a classical example of a genetic region named for its first known function. Studies utilizing antibody typing, mixed lymphocyte reactions (MLRs) and genetic back-crossing (in the mouse) allowed identification of the strong transplantation antigens (class I MHC glycoproteins), then the so-called immune response (Ir) genes that were soon found to encode the MHC class II alleles. A further breakthrough came with the discovery that “self” MHCI and MHCII molecules serve primarily to target killer (CD8+) and helper (CD4+) and T lymphocytes to cells modified by an encounter with some “non-self” protein provided, perhaps, by an infecting virus or bacterium.

Then it was recognized that the primary role of the MHCI and MHCII molecules was to carry processed, non-self peptides to cell-surface for lymphocyte recognition via the cognate TCR, the primary event that triggers CD8+ and CD4+ T lymphocyte clonal expansion and differentiation. Some speculate that there may be a further Nobel prize for elucidating the nature of antigen processing and the key role of the antigen-presenting dendritic cell that triggers “adaptive” immunity. If we had the task of naming the MHC now we would, perhaps, choose to call it the “self-surveillance complex!”

When we also consider the more recent discovery of the KIR/MHC interaction, it is apparent that analysis related in some way or other to the MHC is central to at least half of contemporary immunology. While the analysis of the mouse H₂ and the human HLA systems may to some extent run in parallel, the two areas tend to be pursued by separate laboratories that operate in different contexts. The mouse immunologists generally focus on inbred strains that “fix” one or other MHC haplotype. Dealing as they must with a species that outbreeds, those working with HLA continue to be fascinated by questions related to the extraordinary MHC polymorphism and the association with disease susceptibility profiles.

There is thus a very real place for a new book that updates the field and deals specifically with issues related to “The HLA Complex in Biology and Medicine”. Covering such a broad spectrum would be extraordinarily daunting for any one individual, so the editors have recruited a group of established investigators to summarize their own areas of expertise in a multi-author format. The result is a text that will be invaluable for introducing graduate students to the full spectrum of HLA-related knowledge while serving also as a conceptual and technical source book for both those focused on or other aspect of HLA-related research and clinical/surgical practice. In addition, it will be a primary point of contact for individuals working in other areas who suddenly find that their research is drawing them into the complexities of HLA genetics.

The focus is essentially on the immunological role of HLA and how that relates to infectious disease resistance, autoimmunity and graft and organ transplantation. The present text deals with more practical matters and does not attempt to cover areas of less immediate clinical relevance that may, nonetheless, have broad implications for understanding both mammalian biology and evolution. The latter would be more adequately addressed in a volume that goes beyond human beings and the other placentals to the non-eutherian mammals, birds, bony fish, the lampreys and so forth. Still, there is sufficient conceptual development here to intrigue those with active intellects and draw at least some into the broader implications of MHC genetics.14

This book thus serves those who need to understand how the HLA system impacts on medicine while at the same time providing accounts of practical issues relevant to tissue typing, transplant immunology and clinical immunogenetics. As such, it constitutes an important resource for medical scientists, physicians and surgeons. Given the scope and the undoubted quality of the contributors, it will continue to fulfill those functions in the long-term.

Although the foundations of genomics and immune recognition were laid in the 20th century, the major focus over the next two decades will be in the area of pharmacogenomics, clinical immunogenetics and personalized molecular medicine. The task of screening for potentially thousands of variations in the global population now appears achievable through advanced chip based and mass spectrometric approaches, with the primary focus on single nucleotide polymorphisms (SNPs) that represent point variations between individuals. The HLA-related knowledge coupled with in-depth understanding of the immune mechanisms is the key for achieving tolerance and long-term success in organ and hematopoietic stem cell transplantation.

The HLA system in man was discovered more than 50 years ago, primarily because of the urge to decipher the mechanism of graft rejection. Soon, it became clear that the set of genes within the complex have far more important functions, associated with the overall survival of the species. We decided to compile and produce a comprehensive resource book on the HLA system with particular reference to its role in medicine and biology. The book is planned on the format of a ‘multi-author edited book’ carrying detailed and comprehensive information on almost all aspects of the human MHC including its role in immune response, population diversity, organ and bone marrow transplantation and finally as an efficient biomarker for disease. The publication is meant for postgraduate level students and young researchers seeking authentic information on the above aspects. Indeed, a need for such a publication has been felt for a long time and our endeavor has been to provide the reader with updated information on this rapidly growing subject. For this, we recruited a group of established investigators to cover a wide range of topics.

The publication has been aptly entitled The HLA Complex in Medicine and Biology: A resource Book with four major sections dealing with immune system in general including the cytokine cascade, general features of the human MHC, including population database and nonclassical HLA molecules, MHC and disease associations and a major section dealing with the transplantation issues. Special chapters deal with the History of HLA and its latest nomenclature as we know of in 2009, as well as the biological significance of minor histocompatibility antigens. Similarly, the book carries a detailed description of the killer immunoglobulin-like receptors (KIRs) in health, disease and transplantation. Special emphasis has been given to the section on HLA and disease associations covering particularly the autoimmune, mycobacterial and rheumatological diseases. Separate chapters deal with host determinants in HIV-1 infection and involvement of HLA in drug sensitivity. Similarly, the section on transplantation deals not only with HLA matching strategies for long-term graft survival, but more importantly for antibody analysis, cross-matching and post-transplant antibody monitoring. The book has been designed to introduce the young doctor and researcher to comprehend the role of HLA in hematopoietic stem cell transplantation and the importance of unrelated donor marrow registries.

Many individuals have made invaluable contributions to this rather daunting task. The list of contributors in extensive but we will like to place in record our special thanks to Erik Thorsby, Brian Tait, Steve Marsh, Derek 16Middleton, Antonio Araniz-Villena, Grant Morahan, Mohammed Khan, Veena Taneja, Akinori Kimura, Erwin Schurr, Xiajiang Gao, Sudhir Gupta, Elaine Reed, Els Goulmy, Alejandro Madrigal, Partha Majumdar, Simon and Elizabeth Mallal, Sophie Calliat Zucman, Vijay Kuchroo and Campbell Witt. Our special thanks are due to the excellent team of publishers M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India who have put in a lot of effort to produce a truly international product.

Lastly, we must state that the inspiration for compiling such a resource book came truly from our numerous students and young researchers grappling with defining the mysteries of human MHC. In the words of Peter C Doherty, who discovered the phenomenon of MHC Restriction together with Rolf Zinkernagel way back in the mid-70s, which won them the Nobel prize in 1996, “If we had the task of naming the MHC now we would, perhaps, choose to call it the ‘Self-surveillance complex !’”. The editors are ever grateful to Peter for writing the Foreword of the book. We do hope that the publication will provide the transplant physicians, surgeons, internists and biologists with a clear understanding of the biological meaning of the HLA system and encourage them to decipher its translational role in medicine, and discover its hitherto unmet and unknown aspects.

It has been a wonderful experience building this book. I thank Gurvinder Kaur, who has been an able and indispensible colleague over the years for shouldering a lot of responsibilities to make this project a success. My sincere gratitude to the team of Advisory Editors comprising of Frank C Christiansen, Frans HJ Claas and James McCluskey with whom I have journeyed wonderful years, exploring and learning MHC science, and whose invaluable advice throughout this project helped us develop this unique compendium of appropriate topics and chapters contributed by the very best in this field. Peter C Doherty who won the Nobel prize together with Rolf Zinkernagel in 1996 for defining the biological meaning of the major histocompatibility complex has been gracious in contributing the Foreword for the book. The Editors are ever grateful to him for the same.

My special thanks are to the large number of contributors who readily agreed to our request, despite short notice. Their contributions reflect knowledge, wisdom and lifetime experience. We truly believe that this book will prove immensely useful to students, researchers, teachers and clinicians from various walks of Medicine and Biology. I express my sincere appreciation to Akinori Kimura, Alejandro Madrigal, Antonio Arnaiz-Villena, Brian Tait, Campbell Witt, David Sayer, Derek Middleton, Elaine Reed, Els Goulmy, Erik Thorsby, Erwin Schurr, Frans HJ Claas, Frank C Christiansen, Grant Morahan, Gurvinder Kaur, Simon Mallal, Elizabeth Phillips, Linda Smith, Michael Varney, Sudhir Gupta, Sophie Caillat-Zucman, James McCluskey, Partha Majumder, Suraksha Agrawal, Steven Marsh, Mohammed Asim Khan, Neeraj Kumar, Raja Rajalingam, George Fust, Uma Kanga, Veena Taneja, Vijay Kuchroo, V Mohan, Xiaojiang Gao and their associates for providing their invaluable inputs and for sticking to the time schedule.

This book and indeed every milestone in my career would not have been possible without the active support of my wife, Raj. She and our two children Nikhil and Neha cheerfully accepted my follies and encouraged me to pursue my research and academic activities with vigor and sincerity. Further, the constant support and academic ambience provided by the All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India has been extremely rewarding.

Finally, our appreciation to Shri Jitendar P Vij (Chairman and Managing Director), Mr Tarun Duneja (Director-Publishing) and members of the publishing team, in particular Mr KK Raman (Production Manager) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India who worked continuously for completing this gigantic task in time for release at the ASEATTA 2009 meeting in New Delhi. We do hope that this unique work brought together by some of the most eminent minds in MHC biology will go a long way in encouraging young minds to this fascinating field of science.