Introduction

Even before 1975, when the role of the MHC antigens as a ‘guidance mechanism’ for the immune system was discovered (Zinkernagel & Doherty, 1975), it was known that some tumour cells expressed abnormally low levels of MHC antigens and/or β2-m (Nilsson, Evsin & Welsh, 1974). In addition, there was ample experimental evidence that tumour cells could be ‘recognized’ and eliminated by the immune system, although early work had failed to take into account allogeneic recognition of transplantation antigens (Foley, 1953). By the 1950s it had been clearly shown that chemically induced, radiation-induced and spontaneously occurring tumours could express tumour antigens that could initiate and lead to ‘tumour rejection’, namely the tumour-associated transplantation antigens, TATAs (Gross, 1943). It was only in the late 1970s or early 1980s that these two strands of research could be put together and they have subsequently led to important advances in the clinical treatment of cancer.

These advances are related to the great insight of Paul Ehrlich, who postulated that the immune system acted as a surveillance system to detect changes within the body caused either by normal pathological events or by invading organisms (Ehrlich, 1909). It is now clear that the primary function of CTLs is to monitor cell surfaces for abnormal peptides presented by MHC class I antigens. T cells reactive to normal self peptides will have been made tolerant either by clonal deletion or clonal anergy.