- Email: [email protected]
HLA-G: a new opening for HLA
seminars in C A N C E R B I OL OG Y, Vol 9, 1999: pp. 1 Article No. scbi.1998.0111, available online at http:rrwww.idealibrary.com on
HLA-G: a new opening for HLA J. Dausset† and E. D. Carosella U
HLA-G is a new and spectacular opening in the history of HLA. In fact this history is built of several events. Each one has opened a new perspective, thereby enlarging practical and theoretical interest. The leuco-agglutinin was at first just a simple curiosity, but soon after, the first leucocyte groups were described. At that time they appeared as simple blood groups, of leucocytes and no longer of red blood cells. The first event happened when it was discovered that these groups were not only leucocyte groups but also tissue groups: thus opening the way for organ transplantation and bone marrow transplantation. For many years the HLA laboratories devoted themselves to the use of HLA’s incompatibility for the success of transplantations. The second spectacular event was the demonstration that there exist numerous associations between HLA and disease. Each laboratory then began to search for these associations; the concept of ‘susceptible genes’ was born, thereby opening the way to predictive medicine. The third event was the discovery of HLA antigens of class II and the role they play in immune reactions. This was a fundamental breakthrough which threw a new light on the function of the self defense against the non-self. And now we have a new event, a considerable one. Although HLA-G was described in 1990, it is only in recent years that it has been shown that these molecules are no longer molecules of intolerance, but can have the status of tolerance molecules. And
this despite their size and structure which is very similar to those of classical molecules of intolerance. Recently, a second non-classic molecule called HLA-E was shown to be also capable of inhibiting the NK response. Since then studies of the HLA-G and HLA-E molecules have been going along at full pace. Many laboratories have launched out on its research. During the First International Conference on HLA-G, which was held in Paris in 1998, and which will be renewed in the year 2000, a discussion took place on the role of HLA-G molecules on trophoblasts of placenta villosity, thus forming a barrier between mother and child. The inhibitor action of lymphocytes and NK cells of the mother against the fetal incompatible antigens, is now demonstrated not only in vitro but also ex vivo. Similarly, HLA molecules present on the surface of certain tumor cells could enable these tumors to escape from the immunological reactions of their host. A profound study of inhibitor receptors is one of the major aspects of this new discipline. Eva Klein honored us by requesting that we gather together in this volume the major contributions from the best experts on the subject. She will find here a review of the question in the main areas where these inhibitor molecules seem to be essential for the immunological balance in a normal state. The large scope of recent works show how these molecules can modify future research on transplantation therapy, particularly xenografts and anti-tumoral vaccinations. Thus, from now on the Major Histocompatibility Complex class I is composed of two different antigens: class I classic antigens, which are responsible for identity and defense; and non-classic antigens which are responsible for tolerance. We welcome this new event in an open-minded spirit, with great curiosity and great expectations.
U
From the Service de Recherches en Hemato-Immunologie, CEA ´ r DRM r DSV, Hopital Saint-Louis, Centre Hayem, Institut ˆ d’Hematologie, 1 avenue Claude-Vellefaux, 75475 Paris, Cedex ´ 10, France and †Fondation Jean Dausset, 27, rue Juliette-Dodu, 75010 Paris Cedex, France 䊚1999 Academic Press 1044-579Xr 99r 010001q 01 $30.00r 0
1
HLA-G: a new opening for HLA J. Dausset† and E. D. Carosella U
HLA-G is a new and spectacular opening in the history of HLA. In fact this history is built of several events. Each one has opened a new perspective, thereby enlarging practical and theoretical interest. The leuco-agglutinin was at first just a simple curiosity, but soon after, the first leucocyte groups were described. At that time they appeared as simple blood groups, of leucocytes and no longer of red blood cells. The first event happened when it was discovered that these groups were not only leucocyte groups but also tissue groups: thus opening the way for organ transplantation and bone marrow transplantation. For many years the HLA laboratories devoted themselves to the use of HLA’s incompatibility for the success of transplantations. The second spectacular event was the demonstration that there exist numerous associations between HLA and disease. Each laboratory then began to search for these associations; the concept of ‘susceptible genes’ was born, thereby opening the way to predictive medicine. The third event was the discovery of HLA antigens of class II and the role they play in immune reactions. This was a fundamental breakthrough which threw a new light on the function of the self defense against the non-self. And now we have a new event, a considerable one. Although HLA-G was described in 1990, it is only in recent years that it has been shown that these molecules are no longer molecules of intolerance, but can have the status of tolerance molecules. And
this despite their size and structure which is very similar to those of classical molecules of intolerance. Recently, a second non-classic molecule called HLA-E was shown to be also capable of inhibiting the NK response. Since then studies of the HLA-G and HLA-E molecules have been going along at full pace. Many laboratories have launched out on its research. During the First International Conference on HLA-G, which was held in Paris in 1998, and which will be renewed in the year 2000, a discussion took place on the role of HLA-G molecules on trophoblasts of placenta villosity, thus forming a barrier between mother and child. The inhibitor action of lymphocytes and NK cells of the mother against the fetal incompatible antigens, is now demonstrated not only in vitro but also ex vivo. Similarly, HLA molecules present on the surface of certain tumor cells could enable these tumors to escape from the immunological reactions of their host. A profound study of inhibitor receptors is one of the major aspects of this new discipline. Eva Klein honored us by requesting that we gather together in this volume the major contributions from the best experts on the subject. She will find here a review of the question in the main areas where these inhibitor molecules seem to be essential for the immunological balance in a normal state. The large scope of recent works show how these molecules can modify future research on transplantation therapy, particularly xenografts and anti-tumoral vaccinations. Thus, from now on the Major Histocompatibility Complex class I is composed of two different antigens: class I classic antigens, which are responsible for identity and defense; and non-classic antigens which are responsible for tolerance. We welcome this new event in an open-minded spirit, with great curiosity and great expectations.
U
From the Service de Recherches en Hemato-Immunologie, CEA ´ r DRM r DSV, Hopital Saint-Louis, Centre Hayem, Institut ˆ d’Hematologie, 1 avenue Claude-Vellefaux, 75475 Paris, Cedex ´ 10, France and †Fondation Jean Dausset, 27, rue Juliette-Dodu, 75010 Paris Cedex, France 䊚1999 Academic Press 1044-579Xr 99r 010001q 01 $30.00r 0
1