The identity of minor lymphocyte stimulating (Mls) antigens, endogenous superantigens that can activate, or induce the deletion of, large portions of the T-ceil repertoire, has recently been revealed: they are encoded by mouse mammary tumor viruses (MMTV) that have integrated into the germ line as DNA proviruses. As Hans Acha-Orbea and Ed Palmer point out, Mls-mediated modulation may be only the tip of the retrovirus iceberg; already murine leukemia virus (MuL V), with similar superantigen properties, has been discovered.

The minor lymphocyte stimulating (Mls) antigens were originally discovered by Hilliard Festenstein, who found that vigorous mixed leukocyte reactions (MLR) could be initiated between major histocompatibility complex (MHC)-identical strains of mice. He called these polymorphic differences minor lymphocyte stimulating antigens since they were encoded outside the MHC. Further work showed that the stimulating cells (from Mlspositive mice) are largely B cells while the responding cells (from Mls-negative mice) are T cells 2-5. Genetic studies of Mls at first suggested a single genetic locus with five allelic gene products, but further analysis revealed that the Mls antigens are derived from a number of unlinked loci, each of which encodes a biallelic system 2, 6. One allele from each Mls locus is stimulatory in an MLR while the other allele is not. This is quite different from a typical MHC gene, where each of the alleles is encoded within a single locus and the vast majority of alleles are stimulatory in H-2 alloresponses. Within the past few years Mls nomenclature has been changed (and will likely change again); recent discussions of the Mls gene products assign a number to each genetic locus (for example Mls-I and Mls-2) and the stimulatory allele of each locus is referred to as the'a'haplotype while the nonstimulatory, or null, allele is referred to as the'b'haplotype. In this system of Mls nomenclature, mice that express the functional product of the Mls-1 locus are Mls-1% while mice that do not express a functional Mls-1