The murine B16/BL6 melanoma and all its sublines  are  nonimmunogenic  and  express tow levels  of  MHC  class  I.  Expression of transfected or endogenous H-2K^b gene in BL6 melanoma cells remarkably increased their immunogenecity.  HPLC fractionation of acid eluted  H-2  associated  peptides  helped  to identify five fractions  that  recognized  by  the anti-melanoma CTLs in association with the H- 2K^b  molecules.  On the other hand, BL6 melanoma and its lines also express melanoma associated antigen (MAA) detectable by mAbs MM2-3C6 and MM2-9B6. These mAbs are highly efficient in eradication of B16 melanoma metastasis. Interestingly, increase in immunogenicity of the H-2K^b transfected BL6 melanoma cells was associated with loss of MAA expression. We found that MAA was a retroviral product and was encoded by the env region of a BL6 melanoma associated C-type ecotropic retrovirus (MelARV). Further analysis of the  mechanism of the loss of MAA expression showed that loss of MAA is a result of complete inhibition of retrovirus production. Our data indicate that loss of retroviral production is due to alterations in proviral DNA. Nucleotide sequence analysis of the PCR amplified proviruses in the H-2K^b + and  H-2K^b - BL6   melanoma    cells    suggests    that recombination   between   the   productive ecotropic and defective xenotropic proviruses results   in  the  emergence  of  the  novel proviruses that are responsible for the observed failure to  produce  mature  retroviral  particles and to express MAA. The MelARV emerged somatically from an ecotropic endogenous retrovirus (Emv-2) in melanomas of C57/BL mouse. Its role in melanoma formation and progression remains unknown. To address this question, we   recently   infected   normal melanocytes with the MelARV from the BL6 melanoma cells.  Showing that the MelARV was able to induce malignant transformation of normal melanocytes and this ability to transform melanocytes might be a result of viral insertion and changes in expression of cellular oncogene(s) and/or tumor suppressor gene(s). Flanking sequencing analysis using inverse PCR showed that the 3` end of c-maf proto-oncogene is one of the common insertion sites in these melanoma cells. The novel retrovirus-induced melanomas (Meli-A1 and Meli-BL 1) do not express the MHC class I molecules due to down-regulation of the H-2K^b, H-2D^b and TAP-1 genes. Failure to express MHC class molecules was not due to retrovirus infection or malignant transformation but was inherited from the parental melanocytes that also found to be MHC class I negative. Thus the ecotropic MelARV might play an active role in melanoma formation and progression. This experimental model might serve as a paradigm for analysis of the mechanisms of melanoma formation and MHC-retroviral gene interactions.