The major histocompatibility complex, located on chromosome 6 in man and 17 in the mouse, contains a series of genes encoding transmembrane proteins that play an important role in immune responses. For instance, T-cell mediated cytolysis directed against allodifferences or virally-induced differences (Eij svoogel et al. 1972, Zinkernagel andDoherty 1974) often involves class I molecules (HLA-A, -B, -C in man; H-2K, D, L, Qa in the mouse) that are encoded in this region. Also, susceptibility to certain diseases is statistically associated with particular HLA haplotypes (Svejaard et al. 1980). Molecular analysis of human and mouse class I genes has recently revealed that the number of class I related coding sequences is approximately 20-30 per haploid genome (Cami et al. 1981, Steinmetz et al. 1981a, Steinmetz et al. 198 lb, Orr et al. 1981, Steinmetz et al. 1982). A study of the cloned genes would make it possible to elucidate the organization of the human HLA complex. However, an experimental system is needed to differentiate between functional and pseudo-HLA class I genes, and to permit the serological analysis of the product of an isolated gene. We attempted to transform mouse LMTK-cells with HLA genes in suitable cosmid vectors. Expression of class I determinants has been reported in similar systems with cloned murine H-2 (Goodenow et al. 1982) and porcine SLA (Singer et al. 1982) class I genes. We found that HLA heavy chains can be expressed in mouse cells, that they are present at the cell surface and recognized by anti-HLA class I monoclonal antibodies, that L cells transformed by different cosmids display distinct reactivities with different nonpolymorphic antibodies, and that expression of HLA heavy chains apparently does not reduce the number of endogenous H-2 molecules at the cell surface.
Cosmid clones containing HLA class I genes, isolated by some of us* and illustrated in Figure 1, were used to transform (Wigler et al. 1977(Wigler et al. , 1979) ) LMTK-