Summary
We have isolated cDNA clones from a human NK cell cDNA library that encode the serine protease granzyme B. Although the sequence of the entire coding region for the mature protein and the 3′ untranslated region of the clone are identical to other cDNA isolates of this gene obtained from human T cell cDNA libraries, the 5′ end of two clones is 103 bp longer than the previously described sequences and would encode a protein with a 54-amino-acid-long signal sequence. Experiments characterizing granzyme B mRNA suggest that transcripts that initiate at or before the 5′ end of these clones comprise a detectable but infrequent class of granzyme B transcripts in NK and T cells. We have mapped this gene to human chromosome 14 in the region 14q11→14q32, distal to the T cell receptor alpha locus and proximal to the immunoglobulin heavy chain locus. The chromosomal location of this gene, together with the previously described high sequence homology between this gene and the mouse CTLA1/ccp1 gene, make it likely that this is the human equivalent of the mouse CTLA 1/ ccp1.
Similar content being viewed by others
References
Brunet JF, Dosseto M, Denizot F, Mattei MG, Clark WR, Haqqi TM, Ferrier P, Nabholz M, Schmitt-Verhulst AM, Luciani MF, Golstein P (1986) The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1 sequence and gene localization to mouse chromosome 14. Nature 322:268–271
Cannizzaro LA, Croce CM, Griffen CA, Simeone A, Bonicinelli E, Heubner K (1987) Human homeo box-containing genes located at chromosome regions 2q31→2q37 and 12q12→12q13. Am J Hum Genet 41:1–15
Caputo A, Fahey D, Lloyd C, Vozab R, McCairns E, Rowe P (1988) Structure and differential mechanisms of regulation of expression of a serine esterase gene in activated human T lymphocytes. J Biol Chem 263:6363–6369
Chan WC, Link S, Mawle A, Check I, Brynes RK, Winton EF (1986) Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes. Blood 68:1142–1153
Chan WC, Dahl C, Waldmann T, Link S, Mawle A, Nicholson J, Bach FH, Bongiovanni K, McCue PA, Winton EF (1988) Large granular lymphocyte proliferation: an analysis of T-cell receptor gene arrangement and expression and the effect of in vitro culture with inducing agents. Blood 71:52–58
Chang TW, Eisen HN (1980) Effects of N alpha-tosyl-l-lysyl-chloromethylketone on the activity of cytotoxic T lymphocytes. J Immunol 124:1024–1029
Cochran BH, Reffel AC, Stiles CD (1983) Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell 33:939–947
Croce CM, Isobe M, Palumbo A, Puck J, Erikson J, Davis M, Rovera G (1985) Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. Science 227:1044–1047
Dahl CA, Cairns JS, Chan WC, Bach FH (1989) Isolation of human NK cell and NK/T cell specific cDNA clones. In: Ades EW, Lopez C (eds) Natural killer cells and host defense. (5th International Natural Killer Cell Workshop, Hilton Head, SC 1988) Karger, New York, Basel, pp 12–15
Durst M, Croce CM, Gissman L, Schwarz E, Huebner K (1987) Papillomavirus sequences integrate near cellular oncogenes in some cervical carcinomas. Proc Natl Acad Sci USA 84:1070–1074
Erikson J, Finan J, Nowell PC, Croce CM (1982) Translocation of immunoglobin VH genes in Burkitt lymphoma. Proc Natl Acad Sci USA 79:5611–5614
Gershenfeld HK, Weissman IL (1986) Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte. Science 232:854–858
Gershenfeld HK, Hershberger RJ, Shows TB, Weissman IL (1988) Cloning and chromosomal assignment of a human cDNA encoding T cell- and natural killer cell-specific trypsin-like serine protease. Proc Natl Acad Sci USA 85:1184–1188
Gubler U, Hoffman BJ (1983) A simple and very efficient method for generating cDNA libraries. Gene 25:263–269
Haluska FG, Finver SN, Tsujimoto Y, Croce CM (1986) The t(8;14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining. Nature 324:158–160
Hameed A, Lowrey DM, Lichtenheld M, Podack ER (1988) Characterization of three serine esterases isolated from human IL-2 activated killer cells. J Immunol 141:3142–3147
Heijne G von (1985) Signal sequences: the limits of variation. J Mol Biol 184:99–105
Hohn PA, Popescu NC, Hanson RD, Salvesen G, Croce C (1989) Genomic organization and chromosomal localization of the human cathepsin G gene. J Biol Chem 264:13412–13419
Huebner K, Isobe M, Gasson JC, Golde DW, Croce CM (1986) Localization of the gene encoding human erythroid-potentiating activity to chromosome region Xp11.1→Xp11.4. Am J Hum Genet 38:819–826
Isobe M, Heubner K, Maddon PJ, Littman DR, Axel R, Croce CM (1986) The gene encoding the T-cell surface protein T4 is located on human chromosome 12. Proc Natl Acad Sci USA 83:4399–4402
Krahenbuhl O, Rey C, Jenne D, Lanzavecchia A, Groscurth P, Carrel S, Tschopp J (1988) Characterization of granzymes A and B isolated from granules of cloned human cytotoxic T lymphocytes. J Immunol 1441:3471–3477
Lobe CG, Finlay BB, Paranchych W, Paetkau VH, Bleackley RC (1986) Novel serine proteases encoded by two cytotoxic T lymphocyte-specific genes. Science 232:858–861
Maniatis T, Fritsch EF, Sambrook J (eds) (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Massen D, Nabholz M, Estrae C, Tschopp J (1986) Granules of cytolytic T-lymphocytes contain two serine esterases. EMBO J 5:1595–1600
Purello M, Alhadeff B, Whittingdon R, Buckton KE, Daniel S, Arnaud P, Rocchi M, Archidiacono N, Filippi G, Siniscalco M (1987) Comparison of cytologic and genetic distances between long arm subtelomeric markers of human autosome 14 suggests uneven distribution of crossing-over. Cytogenet Cell Genet 44:32–40
Redelman D, Hudig D (1980) The mechanism of cell-mediated cytotoxicity. I. Killing by murine cytotoxic T lymphocytes requires cell surface thiols and activated proteases. J Immunol 124:870–876
Reed KC, Mann DA (1985) Rapid transfer of DNA from agarose gels to nylon membrane. Nucleic Acids Res 13:7207–7221
Russo G, Isobe M, Pegoraro L, Finan J, Nowell PC, Croce CM (1988) Molecular analysis of a t(7;14)(q35;q32) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia. Cell 53:137–144
Schmid J, Weissmann C (1987) Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogenstimulated human leukocytes. J Immunol 139:250–256
Searle AG, Peters J, Lyon MF, Evans EP, Edwards JH, Buckle VJ (1987) Chromosome maps of man and mouse, III. Genomics 1:3–18
Trapani JA, Klein JL, White PC, Dupont B (1988) Molecular cloning of an inducible serine esterase gene from human cytotoxic lymphocytes. Proc Natl Acad Sci USA 85:6924–6928
Woodbury RG, Everitt M, Sanada Y, Katunuma N, Lagunoff D, Neurath H (1978a) A major serine protease in rat skeletal muscle: evidence for its mast cell origin. Proc Natl Acad Sci USA 75:5311–5313
Woodbury RG, Katunuma N, Kobayashi K, Titani K, Neurath H (1978b) Covalent structure of a group-specific protease from rat small intestine. Biochemistry 17:811–819
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dahl, C.A., Bach, F.H., Chan, W. et al. Isolation of a cDNA clone encoding a novel form of granzyme B from human NK cells and mapping to chromosome 14. Hum Genet 84, 465–470 (1990). https://doi.org/10.1007/BF00195821
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00195821