Genes for control of spread of the tumor and Mycobacterium tuberculosis infection in the mouse.
In this review, new data are interpreted that provide some answers to the question of why the immune system fails to respond to metastatic cancers. A function such as an element of the immune response is expected to be under the control of a gene. To find a gene, a mutant is required. Complex screens have been designed and used to detect mouse mutants resisting spread of transplantable tumors (in a spontaneous metastasis assay). Curiously, both mutants with increased and decreased resistance to spread of the tumor have been found. S-27 is a strongly resistant mutant linked to MHC; this mutation also affected some responses to Mycobacterium tuberculosis infection. A long sought link between malignant transformation and vaccination against mycobacterial diseases is discovered in this mutant. A search for a molecule responsible for effects of the S-27 mutation resulted in an unexpected finding. The S-27 mutant carries complex nucleotide alterations at the junction between the signal sequence and the sequences coding for the mature MHC class II A beta polypeptide chain. Antigen recognition region of the A beta molecule is not affected by this mutation. Some concepts developed during the course of this study are illustrated in Figures 1 to 4.
Egorov
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IK
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Nickonenko
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BV
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005802:Genes, MHC Class II / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*