Marc Feldmann

This book encompasses the proceedings of a conference held at Trinity College, Oxford on September 21-25, 1985 organized by a committee comprised of Drs. M. Crumpton, M. Feldmann, A. McMichael, and E. Simpson, and advised by many friends and colleagues. The immune response gene workshops that took place were based on the need to understand why certain experimental animal strains were high responders and others were low responders. It was assumed that identification of the immune response (Ir) genes and definition of their products would explain high and low responder status. Research in the ensuing years has identified the Ir gene products involved in antibody responses as the la antigens, or MHC Class II antigens. These proteins are now well defined as members of the immunoglobulin gene superfamily, and their domain structure is known. Epitopes have been defined by multiple mono­ clonal antibodies and regions of hypervariability identified. Their genes have been identified and cloned. The basic observation of high and low responsive­ ness to antigen is still not understood in mechanistic terms, however, at either the cellular or molecular level. This is because the rate of progress in immune regulation has been far slower than in the molecular biology of the MHC Class II antigens. This is not surprising, since immune regulation is a very complex field at the crossroads of many disciplines.

This book encompasses the proceedings of a conference held at Trinity College, Oxford on September 21-25, 1985 organized by a committee comprised of Drs. M. Crumpton, M. Feldmann, A. McMichael, and E. Simpson, and advised by many friends and colleagues. The immune response gene workshops that took place were based on the need to understand why certain experimental animal strains were high responders and others were low responders. It was assumed that identification of the immune response (Ir) genes and definition of their products would explain high and low responder status. Research in the ensuing years has identified the Ir gene products involved in antibody responses as the la antigens, or MHC Class II antigens. These proteins are now well defined as members of the immunoglobulin gene superfamily, and their domain structure is known. Epitopes have been defined by multiple mono­ clonal antibodies and regions of hypervariability identified. Their genes have been identified and cloned. The basic observation of high and low responsive­ ness to antigen is still not understood in mechanistic terms, however, at either the cellular or molecular level. This is because the rate of progress in immune regulation has been far slower than in the molecular biology of the MHC Class II antigens. This is not surprising, since immune regulation is a very complex field at the crossroads of many disciplines.

Most complex biological systems, such as enzyme pathways, are effec­ tively controlled near the beginning of the process. There is increasing evidence that the same is true for the immune system, with the initial interactions between antigen, antigen-presenting cells, and T cells hav­ ing a paramount influence on the ensuing events. Thus, analysis of the early stages of the immune responses has been a preoccupation of many immunologists. This has been considerably aided by the capac­ ity to expand these early events, and 'immortalize' them as clones of T cells, for detailed analysis. The discovery by Morgan, Ruscetti, and Gallo (Science 193, 1007, 1976) of T-cell growth factor (now termed interleukin-2 or IL-2) has had a major impact in immunology that is far from over. The greater ease of handling murine tissues experimentally, with the availability of more precisely defined reagents such as inbred strains, has meant that, to date, most of the work on long-term T-cell cultures has been per­ formed in the mouse, as summarized by Fathman and Fitch (eds. , Iso­ lation, Characterization and Utilization of T Lymphocyte Clones, Aca­ demic Press, NY, 1982). However, the limitations of working with human tissues are counterbalanced by the great long-term importance of understanding disorders of human immune regulation, especially since it is becoming evident that these are far from rare. Immune deficiencies such as agammaglobulinemia and T-cell deficiencies are not common, but immune hyperresponsiveness occurring in allergy and allergiC diseases (e. g.

Leukocyte culture conferences have a long pedigree. This volume records some of the scientific highlights of the 16th such annual con­ ference, and is a witness to the continuing evolution and popularity of leukocyte culture and of immunology. There is strong evidence of the widening horizons of immunology, both technically, with the obviously major impact of molecular biology into our understanding of cellular processes, and also conceptually. Traditionally, the 'proceedings' of these conferences have been published. But have the books produced really recorded the major part of the conference, the informal, friendly, but intense and some­ times heated exchanges that take place between workers in tackling very similar problems and systems and which are at the heart of every successful conference? Unfortunately this essence cannot be incorpo­ rated by soliciting manuscripts. For this reason, we have changed the format of publication, retaining published versions of the symposium papers, but requesting the workshop chairmen to produce a summary of the major new observations and areas of controversy highlighted in their sessions, as a vehicle for defining current areas of interest and debate. Not an easy task, as the workshop topics were culled from the abstracts submitted by the participants, rather than being on predefined topics. The unseasonal warmth in Cambridge was reflected in the atmos­ phere of the conference, the organization of which benefited from the administrative skills of Jean Bacon, Philippa Wells, Mr. Peter Irving, and Mrs.

Most complex biological systems, such as enzyme pathways, are effec­ tively controlled near the beginning of the process. There is increasing evidence that the same is true for the immune system, with the initial interactions between antigen, antigen-presenting cells, and T cells hav­ ing a paramount influence on the ensuing events. Thus, analysis of the early stages of the immune responses has been a preoccupation of many immunologists. This has been considerably aided by the capac­ ity to expand these early events, and 'immortalize' them as clones of T cells, for detailed analysis. The discovery by Morgan, Ruscetti, and Gallo (Science 193, 1007, 1976) of T-cell growth factor (now termed interleukin-2 or IL-2) has had a major impact in immunology that is far from over. The greater ease of handling murine tissues experimentally, with the availability of more precisely defined reagents such as inbred strains, has meant that, to date, most of the work on long-term T-cell cultures has been per­ formed in the mouse, as summarized by Fathman and Fitch (eds. , Iso­ lation, Characterization and Utilization of T Lymphocyte Clones, Aca­ demic Press, NY, 1982). However, the limitations of working with human tissues are counterbalanced by the great long-term importance of understanding disorders of human immune regulation, especially since it is becoming evident that these are far from rare. Immune deficiencies such as agammaglobulinemia and T-cell deficiencies are not common, but immune hyperresponsiveness occurring in allergy and allergiC diseases (e. g.

Leukocyte culture conferences have a long pedigree. This volume records some of the scientific highlights of the 16th such annual con­ ference, and is a witness to the continuing evolution and popularity of leukocyte culture and of immunology. There is strong evidence of the widening horizons of immunology, both technically, with the obviously major impact of molecular biology into our understanding of cellular processes, and also conceptually. Traditionally, the 'proceedings' of these conferences have been published. But have the books produced really recorded the major part of the conference, the informal, friendly, but intense and some­ times heated exchanges that take place between workers in tackling very similar problems and systems and which are at the heart of every successful conference? Unfortunately this essence cannot be incorpo­ rated by soliciting manuscripts. For this reason, we have changed the format of publication, retaining published versions of the symposium papers, but requesting the workshop chairmen to produce a summary of the major new observations and areas of controversy highlighted in their sessions, as a vehicle for defining current areas of interest and debate. Not an easy task, as the workshop topics were culled from the abstracts submitted by the participants, rather than being on predefined topics. The unseasonal warmth in Cambridge was reflected in the atmos­ phere of the conference, the organization of which benefited from the administrative skills of Jean Bacon, Philippa Wells, Mr. Peter Irving, and Mrs.