Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex

Tumour necrosis factor (TNF-α) and lymphotoxin (TNF-β) are related proteins, secreted by macrophages and lymphocytes respectively, which play a role in destruction of tumour cells and virally infected cells (for reviews see refs 1, 2). TNF-α is a non-glycosy-lated protein of relative molecular mass 17,000 (M_r 17 K), whereas TNF-β is a glycoprotein of M_r25K. Both TNF-α and TNF-β aggregate into multimers and act through the same receptor molecule on target cells. Genes encoding these two TNF proteins have been cloned from mouse and man^3-6 and in both are closely linked, being separated by ∼1 kilobase (kb) of DNA ^7,8. In the mouse these genes are located on chromosome 17 (ref. 8), but in man they are on the short arm of chromosome 6 (ref. 9). This segment of chromosome 6 also contains the genes of the major histocompatibility complex (MHC), as does chromosome 17 in the mouse. To find out whether the TNF genes are located within the MHC, we used polymorphic restriction sites to analyse a panel of MHC congeneic and intra-MHC recombinant mouse strains. Initially, we mapped the TNF genes the D or Qa region in the distal half of the mouse MHC. We then studied a gene cluster encompassing part of the D and Qa regions and found the TNF genes are located 70 kb proximal to the D gene.