A clone (pHLA-1) containing HLA-specific cDNA was constructed by reverse transcription of partially purified HLA mRNA from the human Imphoblastoid cell line LKT. The identity of pHLA-1 was established by its ability to hybridize to HLA heavy chain mRNA and by nucleotide sequence analysis. The pHLA-1 cDNA insert (-525 base pairs) corresponds to the COOH-terminal 46 amino acids of an HLA-A, -B, or -C antigen (15 residues from the hydrophobic region and the remainder from the COOH-terminal hydrophilic region), together with a portion of the 3' untranslated region of the mRNA.The major histocompatibility complex (MHC) is located on the short arm of chromosome 6 in man (1), and includes the HLA system. This genetic region encodes a series of highly polymorphic membrane glycoproteins, the HLA antigens, in addition to components of the complement system, all of which are of crucial importance to a proper functioning of the immune system (2). In addition to the high degree of polymorphism that these MHC products display, the association of certain alleles at HLA loci with a large number of human diseases is of considerable interest (3). The definition of the genetic and mechanistic bases for these disease associations and the evolutionary origin of the polymorphism that may relate to the function(s) of these molecules are most intriguing biological questions.The classic histocompatibility antigens-i.e., those antigens that are targets for graft rejection-are encoded by the HLA-A, -B, and -C loci. At present, 20, 40, and 8 alleles have been defined at these loci, respectively (4). The number of alleles defined serologically must necessarily represent a minimum estimate of the actual number of alleles present in the human population. A major goal in the structural studies on HLA antigens* has been to relate their complex genetic and serologic properties with structure and function. Amino acid sequence studies of HLA-B7 have provided a molecular description of this antigen (5-9), and comparison of its sequence with partial sequences of other specificities has yielded some insight into the question of regions of allelic variation (10). However, a correlation of primary structure with serologic and functional properties will require the collection of an extensive amount of sequence information. Approaching this problem through determination of the amino acid sequence of a large number of allelic HLA antigens would represent a prodigious effort. Moreover, a purely protein chemical approach cannot address directly some of the fundamental questions concerning the genomic organization of the MHC that are important in understanding the HLA system in detail.Reported here is the molecular cloning of an HLA-specific cDNA fragment. This cloned fragment provides a tool for the selection and purification of HLA-specific mRNA and can be used as a probe in the isolation of other HLA cDNA clones, thus making the HLA system amenable to analysis by molecular biological methods. Compared to amino acid sequence determination, the dete...