Avrion (Av) died peacefully on 28 December 2022, aged 94. He was husband to Lorna, father to Tim, Mary, Matthew, Hannah and Ellen, and a proud ceannard to a large clan of grandchildren, whom he adored.
Av was the son of a Labour politician (Gilbert ‘Dick’ Mitchison) and the writer Naomi Mitchison (née Haldane), nephew to prominent geneticist J. B. S. Haldane, and grandson of the physiologist John Scott Haldane. With such a provenance, Av joked that he simply ‘went into the family business’ and became a scientist in Oxford under the guidance of Peter Medawar. Initially as a lecturer and then a reader at the University of Edinburgh (pictured above) and later as head of the Experimental Biology Division at the National Institute of Medical Research (NIMR), Av initiated a series of experiments that collectively provided the conceptual framework of much of today’s understanding of immune rejection, tolerance and T–B cell co-operation. Av realized that B cells require T cell help to produce specific antibodies, and in now classic experiments, he demonstrated that B and T cells interact by recognizing different parts of an immunogen. One part — the ‘hapten’ — contained the B cell epitope, and the other — the ‘carrier’ — contained the T cell epitope. Clear evidence for this came from the finding that a mouse primed by injection of a hapten-carrier conjugate makes a full secondary antibody response only to the hapten as part of the same conjugate, but not to a hapten conjugated to a different carrier. This showed that two cells were involved, one recognizing the hapten and the other the carrier. Crucially, the hapten and the carrier had to be physically linked for a productive interaction between B and T cells to occur2 and to explain this, Av imagined that B and T cells interacted simultaneously with different parts of the antigen via an ‘antigen bridge’. We now know that T cell receptors interact with processed antigen fragments presented by major histocompatibility complex (MHC) molecules3 and that for this cooperation to occur, antigens must first be internalized and processed by hapten-specific B cells, and carrier epitopes presented on the surface of B cells in association with MHC molecules4.
