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Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T cell
Abstract:
The immunological surveillance hypothesis was formulated prior to the realization of the fact that an individual's effector T cells generally only see neoantigen if it is appropriately presented in the context of self MHC glycoproteins. The biological consequence of this mechanism is that T lymphocytes are focused onto modified cell-surface rather than onto free antigen. The discovery of MHC-restricted T cell recognition, and the realization that T cell-mediated immunity is of prime importance in promoting recovery from infectious processes, has thus changed the whole emphasis of the surveillance argument. Though the immunological surveillance hypothesis generated considerable discussion and many good experiments, there is no point in continuing the debate in the intellectual context that seemed reasonable in 1970. It is now much more sensible to think of "natural surveillance" and "T cell surveillance," without excluding the probability that these two systems have elements in common. We can now see that T cell surveillance probably operates well in some situations, but is quite ineffective in many others. Part of the reason for this may be that the host response selects tumor clones that are modified so as to be no longer recognized by cytotoxic T cells. The possibility that this reflects changes in MHC phenotype has been investigated, and found to be the case, for some experimental tumors. In this regard, it is worth remembering that many "mutations" in MHC genes that completely change the spectrum of T cell recognition are serologically silent. The availability of molecular probes for investigating the status of MHC genes in tumor cells, together with the capacity to develop cloned T cell lines, monoclonal antibodies to putative tumor antigens, and cell lines transfected with genes coding for these molecules, indicates how T cell surveillance may profitably be explored further in both experimental and human situations.