| Citation | Distinguished for his contributions to understanding the ontogeny, specificity and effector functions of cytotoxic T lymphocytes. In 1975 he showed that the response to minor histocompatibility antigens is restricted by the major histocompatibility complex (MHC) as previously found for virus-infected or chemically modified cells. Hence MHC restriction is a general phenomenon encompassing normal unmodified cells. He next established that one and the same T cell is specific for both foreign MHC and for self MHC-plus-antigen and also that foreign antigen and MHC interact with the same receptor on cloned T cells (the 'altered self' concept). He discovered that the specificity repertoire of T cells is selected in the thymus by self MHC-encoded antigens. Cytotoxic T cells were also shown to be capable of switching off responses directed against their own surface antigens - an effect relevant to the maintenance of self-tolerance. Most recently, he has demonstrated circumvention of MHC restriction by means of hybrid monoclonal antibodies where one anti-T cell receptor site can focus the cells to act against an antigen identified by the other antibody site. |