Class I-like HLA genes map telomeric to the HLA-A2 locus in human cells

Abstract

Among the proteins encoded by the major histocompatibility complex (MHC) are the highly polymorphic class I major transplantation antigens, HLA-A and HLA-B in man and H–2K and H–2D in mouse. Class I loci also include the less polymorphic HLA-C in man and H–2L in mouse. Class I antigens are 45,000-molecular weight (M_r) glycosylated membrane proteins associated on the cell surface with apparently nonpolymorphic β₂-microglobulin¹. Linked to the murine MHC are genes encoding the class I-like Qa and Tla antigens, which are closely related structurally to H–2K, D and L, as they are also 45,000-M_r cell surface glycoproteins associated with β₂-microglobulin^2–7. Such class I molecules have also been found on the surface of human T lymphocytes^8–11 and, in one case, shown to be linked to HLA-A¹². Recombinant DNA techniques have been used to map DNA fragments to the Tla region in mouse^13,14. A similar genetic analysis of the HLA complex is hampered by the lack of congeneic strains and by the small number of intra-MHC recombinants in well studied families. One means of overcoming these problems involves a molecular genetic analysis of human lymphoblastoid cell line (LCL) mutants¹⁵ having γ-ray-induced physical deletions of HLA DNA to map DNA fragments in the MHC¹⁶. Here we have applied this method to provide evidence that some human class I-like DNA sequences are telomeric to the A2 locus in LCL 721.