BriefDefinitive Report Mls IS NOT A SINGLE GENE, ALLELIC SYSTEM Different Stimulatory Mls Determinants Are the Products of at Least Two Nonallelic, Unlinked Genes

The set of cell surface determinants encoded by the MHC is remarkable in that it is recognized by naive T cell populations at a sufficiently high precursor frequency to induce substantial primary proliferative responses, and the critical biologic role played by MHC products has been well established . The only other determinants capable of inducing strong proliferative responses by naive T cells have been identified in the mouse as minor lymphocyte stimulating (Mls) gene products (1, 2) . It was originally proposed by Festenstein that Mls is a single gene system mapped to chromosome 1 (3), and that the Mls locus has at least four alleles, a, b, c, and d (1), which encode polymorphic cell surface structures on B cells and macrophages . Subsequent studies have documented the extraordinarily high frequency of Mlsaor Mlsd-reactive T cells encountered in both naive (2) and cloned T cell populations (4) . In spite of its initial characterization, the issues of polymorphism and allelism in the Mls system are matters of significant controversy . Because ofa high degree of observed crossreactivity between Mlsa and Mlsd determinants (5-7) and the nonexistent or weak stimulatory ability of Mlsb and Mls` stimulators, some investigators (7) have suggested that the Mls locus has only two alleles, the "a/d" allele encoding nonpolymorphic determinants which cause strong MLR, and the nonstimulatory or null "b" allele . Based on this interpretation, it has recently been proposed that the Mls gene encodes molecules that cause nonspecific mitogenic stimulation to T cells (7) or that Mls products are nonpolymorphic cell interaction structures that are of generalized importance in influencing the interaction between APCs and responding T cells (8) . In an attempt to better define polymorphism and allelism in the Mls system, studies were initiated using cloned T cells specific for each of the stimulatory Mls alleles . These studies demonstrated that Mlsa and Mls` determinants as recognized by cloned T cells are reciprocally non-crossreactive, indicating that polymorphism does indeed exist in the Mls system (9). More strikingly, it was also found that Mlsd strains coexpress both Mlsa-like and Mls`-like determinants, and that these two sets of determinants are encoded by unlinked genes in the Mlsd genome (10) . These