RESUMO
A single observation in a patient with an unusual transfusion reaction led to a life-long fascination with immunogenetics, and a strong wish to improve the care for patients needing a transplantation. In 2017, Jon van Rood, one of the pioneers in the field of HLA and immunogenetics of transplantation, passed away. Several obituaries have appeared describing some of the highlights of his career. However, the details of the early developments leading among others to the routine use of HLA as an important parameter for donor selection in organ- and hematopoietic stem cell transplantation are largely unknown to the community. After his retirement as Chair of the Department of Immunohaematology and Blood Transfusion (IHB) in 1991, Jon van Rood wrote regularly in the "Crosstalk", the departmental journal, and gave his personal view on the history of the discovery and implications of HLA. These autobiographic descriptions were originally written in Dutch and have been translated, while texts from other sources and the relevant references have been added to illustrate the historical perspective. This special issue of Transplant Immunology combines the autobiographic part, Jon's own version of the history, with other facts of his scientific life and the impact of his findings on the field of clinical transplantation. Hopefully, this knowledge of the history will be of benefit for future developments in transplantation immunology.
Assuntos
Antígenos HLA/imunologia , Imunogenética/história , Imunologia de Transplantes , Transfusão de Sangue , Transplante de Células-Tronco Hematopoéticas , História do Século XX , História do Século XXI , HumanosRESUMO
T cell discrimination of self and non-self is predicated on αß T cell receptor (TCR) co-recognition of peptides presented by MHC molecules. Over the past 20 years, structurally focused investigations into this MHC-restricted response have provided profound insights into T cell function. Simultaneously, two models of TCR recognition have emerged, centred on whether the TCR has, through evolution, acquired an intrinsic germline-encoded capacity for MHC recognition or whether MHC reactivity is conferred by developmental selection of TCRs. Here, we review the structural and functional data that pertain to these theories of TCR recognition, which indicate that it will be necessary to assimilate features of both models to fully account for the molecular drivers of this evolutionarily ancient interaction between the TCR and MHC molecules.
Assuntos
Complexo Principal de Histocompatibilidade , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Animais , Diversidade de Anticorpos , Evolução Molecular , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe II/genética , História do Século XX , História do Século XXI , Humanos , Imunogenética/história , Modelos Genéticos , Modelos Imunológicos , Modelos Moleculares , Receptores de Antígenos de Linfócitos T/química , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Biologia de Sistemas , Linfócitos T/imunologiaRESUMO
Early in their study it was recognized that the genes encoding the HLA molecules were highly polymorphic and that there was a need for a systematic nomenclature. The result was the WHO Nomenclature Committee for Factors of the HLA System, which first met in 1968, and laid down the criteria for successive meetings. This committee meets regularly to discuss issues of nomenclature and has published 16 major reports documenting firstly the HLA antigens and more recently the genes and alleles. The standardization of HLA antigenic specificities has been controlled by the exchange of typing reagents and cells in the International Histocompatibility Workshops. Since 1989 when a large number of HLA allele sequences were first analysed and named, the job of curating and maintaining a database of sequences has been of prime importance. In 1998 the IMGT/HLA database became the official repository for HLA sequences. In addition to the nucleotide and protein sequences the database contains information of the cell from which the sequence was obtained. The database which provides tools for sequence analysis and the submission of new data, is updated quarterly and now contains over 1500 HLA allele sequences.
Assuntos
Bases de Dados Genéticas , Antígenos HLA/genética , Biologia Computacional , Bases de Dados Genéticas/história , História do Século XX , História do Século XXI , Humanos , Imunogenética/história , Imunogenética/estatística & dados numéricos , Agências Internacionais/história , Terminologia como AssuntoRESUMO
The paper reconstructs the scientific career of Ruggero Ceppellini, focusing especially on his role in the discovery of the genetic system underlying the Human Leucocyte Antigen. From his earliest investigations in blood group genetics, Ceppellini quickly became an internationally acknowledged authority in the field of immunogenetics--the study of genetics by means of immunological tools--and participated to the endeavor that ultimately yelded a new meaning for the word: thanks to the pioneering research in the HLA field, immunogenetics became the study of the genetic control of immune system. The paper will also place Ceppellini's scientific work against the backdrop of the modernization of Italian genetics after WWII, resulting from the efforts of a handful of scientists to connect to international networks and adopting new methodologies in life sciences.
Assuntos
Antígenos HLA/história , Imunogenética/história , Cooperação Internacional/história , Mudança Social/história , Pesquisa Biomédica/história , Tipagem e Reações Cruzadas Sanguíneas/história , Genética Médica/história , Antígenos HLA/genética , História do Século XX , Humanos , Itália , Malária/genética , Seleção Genética , II Guerra MundialRESUMO
George S. Eisenbarth will remain in our memories as a brilliant scientist and great collaborator. His quest to discover the cause and prevention of type 1 (autoimmune) diabetes started from building predictive models based on immunogenetic markers. Despite his tremendous contributions to our understanding of the natural history of pre-type 1 diabetes and potential mechanisms, George left us with several big questions to answer before his quest is completed.