NORMAL AND ABNORMAL CELL SURFACE GENETICS

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The title of this application comes from a review written in 1969 (84) and refers to the field of research which concerns itself with relating the genome as a whole to the composition of cell surfaces, principally on the initial basis of antigenic systems defined on normal or malignant cells by serological immunogenetics. The period covered in the narrative begins in 1957 when the only pertinent system known except for blood groups was H-2, itself first serologically defined as a blood group. During the next decade it became clear from the new systems described that the serological antigenic composition of tumor cell surfaces includes three categories, representing cellular genes expressed selectively by the cell lineage to which a given tumor belongs, cellular genes abnormally expressed by tumor cells, and partially or completely expressed retroviral genomes. In apparent contradiction of transplantation theory of the times, the new systems all displayed selective expression according to cell lineage. An account is given of how the systems that comprise T cell programs for surface phenotypes eventuated in applications to theoretical and practical immunology. Arguments stemming from the generality of lineage-specific cell surface phenotypes and inferred antiquity of the determining programs are presented in the contexts of development and phylogeny. Contrary to principles of functional differentiation, induction of expression of the multigene program for thymocyte surface phenotype is found to occur in vitro prior to cell division. Theoretical and practical implications of such induction assay methods with respect to hormonal and other inducers and to development in general are indicated, together with notes on the special place of the Tla system in this and other gene- regulatory situations that include irregular expression by leukemias. The systems used for illustration in the text are chosen for their particular value or promise and with a view to signifying applications of molecular biology that are closest to the central aims of this laboratory in understanding the physiology and pathology of cell surface phenotypes. In that connection a point is made that while biochemistry and cellular immunology, and latterly molecular biology, continue to be vital adjuncts, something more may be required before the potentially crucial aspect of supramolecular presentation can be practically assessed.