A 50-year retrospective: cell-mediated immunity and the major histocompatibility complex

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HE AREA in which I was most involved in transplantation is best summarized by focusing on the cellmediated immune responses to antigens of the major histocompatibility complex (MHC). Many of these reminiscences are discussed in the text of my Medawar Lecture, which is also included in this volume. In the period around 1960, one could appreciate from the work of Gowans, Brent, Medawar and others that lymphocytes were both the cells that expressed the transplantation antigens and that responded to those antigens. Thus, in an attempt to develop an in vitro model of the then-called homograft (now, allograft) reaction, I mixed lymphocytes of two individuals in the hope that the antigens on the cells of each would stimulate the lymphocytes of the other to form blasts and divide. This was the result obtained and was the initiation of the mixed leukocyte culture (MLC) test, 1 from which we then developed a one-way MLC test, 2 in which the stimulating cells of the potential donor were treated with either mitomycin-C or x-irradiation. 3 The one-way MLC test has been used as a histocompatibility test to match donor and recipient and has become the basis for in vitro studies of alloimmunity since. I found that one of four sibling pairs failed to stimulate each other in MLC, and there was a single polymorphic locus that controlled reactivity in MLC. 4 With Bernard Amos, we were able to show that the MLC test was controlled by the same locus that controlled the serologically defined antigens being studied by Amos, Payne, van Rood, Dausset, and others. We suggested that this was the major histocompatibility complex in humans based on skin graft experiments that each of us had performed and on the observations that in other species the MHC controlled