Faculty Research 1990 - 1999

Title

Genes for control of spread of the tumor and Mycobacterium tuberculosis infection in the mouse.

Document Type

Article

Publication Date

1994

Keywords

Animal, Base-Sequence, Genes-MHC-Class-II: ge, Mice, Mice-Inbred-C57BL, Molecular-Sequence-Data, Mycobacterium-tuberculosis: im, Neoplasms-Experimental: im, pc, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Tuberculosis: im, pc

JAX Source

Crit Rev Immunol 1994;14(3-4):337-53

Grant

AI35248/AI/NIAID

Abstract

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.

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