Abstract
Transporters associated with antigen processing molecules (TAP1 and TAP2) mediate the transfer of cytosolic peptides into the lumen of the endoplasmic reticulum for association with newly synthesized class I molecules of the major histocompatibility complex. Previous molecular and functional analyses of rat and humanTAP2 homologues indicated major differences in gene diversification patterns and selectivity of peptides transported. Therefore, in this study, we analyzed the alleles of the gorillaTAP2 locus to determine whether the pattern of diversification resembled that in either of those two species. Sequence analysis of theTAP2 cDNAs from gorilla Epstein-Barr virus-transformed B-cell lines revealed four alleles with a genetic distance of less than 1%. The nucleotide substitutions distinguishing the alleles are confined to the 3′ half of the coding region and occur individually or within two small clusters of variability. Diversification of the locus appears to have resulted from point substitutions and recombinational events. Evolutionary-rate estimates for theTAP2 gene in gorilla and human closely approximate those observed for other hominoid genes. The amino acid polymorphisms within the gorilla molecules are distinct from those in the human homologues. The absence of ancestral polymorphisms suggests that gorilla and humanTAP2 genes have not evolved in a trans-species fashion but rather have diversified since the divergence of the lineages.
Similar content being viewed by others
References
Androlewicz, M. J., Anderson, K. S., and Cresswell, P. Evidence that transporters associated with antigen processing translocate a major histocompatibility complex class I-binding peptide into the endoplasmic reticulum in an ATP-dependent manner.Proc Natl Acad Sci USA 90: 9130–9134, 1993
Attaya, M., Jameson, S., Martinez, C. K., Hermel, E., Aldrich, C., Forman, J., Fischer Lindahl, K., Bevan, M. J., and Monaco, J. J. HAM-2 corrects the class I antigen-processing defect in RMA-S cells.Nature 355: 647–649, 1992
Bahram, S., Arnold, D., Bresnahan, M., Strominger, J. L., and Spies, T. Two putative subunits of a peptide pump encoded in the human major histocompatibility complex class II region.Proc Natl Acad Sci USA 88: 10094–10098, 1991
Beck, S., Kelly, A., Radley, E., Khurshid, F., Alderton, R. P., and Trowsdale, J. DNA sequence analysis of 66 kb of the human MHC class II region encoding a cluster of genes for antigen processing.J Mol Biol 228: 433–441, 1992
Cano, P. and Baxter-Lowe, L. A. Novel human TAP2*103 allele shows further polymorphism in the ATP-binding domain.Tissue Antigens 45: 139–142, 1995
Colonna, M., Bresnahan, M., Bahram, S., Strominger, J. L., and Spies, T. Allelic variants of the human putative peptide transporter involved in antigen processing.Proc Natl Acad Sci USA 89: 3932–3936, 1992
Currier, S. J., Ueda, K., Wilingham, M. C., Pastan, I., and Gottesman, M. M. Deletion and insertion mutants of the multidrug transporter.J Biol Chem 264: 14376–14381, 1989
Cutting, G. R., Kasch, L. M., Rosenstein, B. J., Zielenski, J., Tsui, L. C., Antonarakis, S. E., and Kazazian, H. H. A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.Nature 346: 366–369, 1990
Deverson, E. V., Gow, I. R., Coadwell, W. J., Monaco, J. J., Butcher, G. W., and Howard, J. C. MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters.Nature 348: 738–741, 1990
Ennis, P. D., Zemmour, J., Salter, R. D., and Parham, P. Rapid cloning of HLA-A,B cDNA using the polymerase chain reaction.Proc Natl Acad Sci. USA 87: 2833–2837, 1990
Genetics Computer Group.Program Manual for the Wisconsin Package, ver. 8. Madison, Wisconsin, September, 1994
Heemels, M.-T., Schumacher, T. N. M., Wonigeit, K., and Ploegh, H. L. Peptide translocation by variants of the transporter associated with antigen processing.Science 262: 2059–2063, 1993
Higgins, C. F. ABC transporters: from microorganisms to man.Annu Rev Cell Biol 8: 67–113, 1992
Jackson, D. G. and Capra, J. D. TAP2 association with insulin-dependent diabetes mellitus is secondary to HLA-DQB1.Hum Immunol 43: 57–65, 1995
Janke, A., Feldmaier-Fuchs, G., Thomas, W. K., von Haeseler, A., and Pääbo, S. The marsupial mitochondrial genome and the evolution of placental mammals.Genetics 137: 243–256, 1994
Joly, E., Deverson, E. V., Coadwell, J. W., Gunther, E., Howard, J. C., and Butcher, G. W. The distribution ofTap2 alleles among laboratory ratRT1 haplotypes.Immunogenetics 40: 45–53, 1994
Kelly, A., Powis, S. H., Kerr, L.-A., Mockridge, I., Elliott, T., Bastin, J., Uchanska-Ziegler, B., Ziegler, A., Trowsdale, J., and Townsend, A. Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex.Nature 355: 641–644, 1992
Kleijmeer, M. J., Kelly, A., Geuze, H. J., Slot, J. W., Townsend, A., and Trowsdale, J. Location of MHC-encoded transportern in the endoplasmic reticulum and cis-golgi.Nature 357: 342–344, 1992
Klein, J. Generation of diversity at MHC loci: implications for T cell receptor repertions.In M. Fougereau and J. Dausset (eds.):Progress in Immunology IV Immunology 80, Academic Press. London, 1980
Klein, J. Origin of major histocompatibility complex polymorphisms. The trans-species hypothesis.Hum Immunol 19: 155–162, 1987
Kumar, S., Tamura, K., and Nei, M.,MEGA Molecular Evolutionary Genetics Analysis, ver. 1.0, The Pennsylvania State University, University Park, PA, 1993
Li, W.-H. and Graur, DFundamentals of Molecular Evolution, p. 67, Sinauer Associates, Inc., Sunderland, Massachusetts, 1991
Li, W.-H. and Tanimura, M. The molecular clock runs more slowly, in man than in apes and monkeys.Nature 326: 93–96, 1987
Lobigs, M. and Mullbacher, A. Recognition of vaccinia virus-encoded major histocompatibility complex class I antigens by virus immune cytotoxic T cells is independent of the polymorphism of the peptide transporters.Proc Natl Acad Sci USA 90: 2676–2680, 1993
Lobigs, M., Rothenfluh, H. S., Blanden, R. V., and Mullbacher, A. Polymorphic peptide transporters in MHC class I monomorphic Syrian hamster.Immunogenetics 42: 398–407, 1995
Momburg, F., Ortiz-Navarrete, V., Neefjes, J., Goulmy, E., van de Wal, Y., Spits, H., Powis, S. J., Butcher, G. W., Howard, J. C., Walden, P., and Hammerling, G. J. Proteasone subunits encoded by the major histocompatibility complex are not essential for antigen presentation.Nature 360: 174–177, 1992
Momburg, F., Roelse, J., Howard, J. C., Butcher, G. W., Hammerling, G. J., and Neefjes, J. J. Selectivity of MHC-encoded peptide transporters from human, mouse and rat.Nature 367: 648–651, 1994
Monaco, J. J., Cho, S., and Attaya, M. Transport protein genes in the murine MHC: possible implications for antigen processing.Science 250: 1723–1726, 1990
Neefjes, J. J., Momburg, F., and Hammerling, G. J. Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter.Science 261: 769–771, 1993
Obst, R., Armandola, E. A., Nijenhuis, M., Momburg, F., and Hammerling, G. J. TAP polymorphism does not influence transport of peptide variants in mice and humans.Eur J Immunol 25: 2170–2176, 1995
Parham, P., Adams, E. J., and Arnett, K. L. The origins of HLA-A, B, C polymorphism.Immunol Rev 143: 141–180, 1995
Payne, G. M., Spudich, E. N., and Ames, G. F. A mutational hot-spot in the hisM gene of the histidine transport operon in Salmonella typhimurium is due to deletion of repeated sequences and results in an altered specificity of transport.Mol Gen Genet 200: 493–496, 1985
Powis, S. H., Mockridge, I., Kelly, A., Kerr, L.-A., Glynne, R., Gileadi, U., Beck, S., and Trowsdale, J. Polymorphism in a second ABC transporter gene located within the class II region of the human major histocompatibility complex.Proc Natl Acad Sci USA 89: 1463–1467, 1992
Powis, S. H., Tonks, S., Mockridge, I., Kelly, A. P., Bodmer, J. G., and Trowsdale, J. Alleles and haplotypes of the MHC-encoded ABC transportersTAP1 andTAP2.Immunogenetics 37: 373–380, 1993
Powis, S. J., Townsend, A. R. M., Deverson, E. V., Bastin, J., Butcher, G. W., and Howard, J. C. Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter.Nature 354: 528–531, 1991
Powis, S. J., Deverson, E. V., Coadwell, W. J., Ciruela, A., Huskisson, N. S., Smith, H., Butcher, G. W., and Howard, J. C. Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule.Nature 357: 211–215, 1992
Ruvolo, M., Disotell, T. R., Allard, M. W., Brown, W. M., and Honeycutt, R. L. Resolution of the African hominoid trichotomy by use of a mitochondrial gene sequence.Proc Natl Acad Sci USA 88: 1570–1574, 1991
Safa, A. R., Stern, R. K., Choi, K., Agresti, M., Tamai, I., Mehta, N. D., and Roninson, I. B. Molecular basis of preferential resistance to colchicine in multidrug-resistant human cells conferred by Gly-185→Val-185 substitution in P-glycoprotein.Proc Natl Acad Sci USA 87: 7225–7229, 1990
Sambrook, J., Fritsch, E. F., and Maniatis, T.Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, 1989
Shepherd, J. C., Schumacher, T. N. M., Ashton-Rickardt, P. G., Imaeda, S., Ploegh, H. L., Janeway, C. A., and Tonegawa, S. TAP-1 dependent peptide translocation in vitro is ATP dependent and peptide selective.Cell 74: 577–584, 1993
Spies, T., Bresnahan, M., Bahram, S., Arnold, D., Blanck, G., Mellins, E., Pious, D., and DeMars, R. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway.Nature 348: 744–747, 1990
Spies, T. and DeMars, R. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter.Nature 351: 323–324, 1991
Spies, T., Cerundolo, V., Colonna, M., Cresswell, P., Townsend, A., and DeMars, R. Presentation of viral antigen by MHC class I molecules is dependent on a putative peptide transporter heterodimer.Nature 355: 644–646, 1992
Trowsdale, J., Hanson, I., Mockridge, I., Beck, S., Townsend, A., and Kelly, A. Sequences encoded in the class II region of the MHC related to the “ABC” superfamily of transporters.Nature 348: 741–744, 1990
Wright, K. L., White, L. C., Kelly, A., Beck, S., Trowsdale, J., and Ting, J. P.-Y. Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter.J Exp Med 181: 1459–1471, 1995
Yang, Y., Fruh, K., Chambers, J., Waters, J. B., Wu, L., Spies, T., and Peterson, P. A. Major histocompatibility complex (MHC)-encoded HAM2 is necessary for antigenic peptide loading onto class 1 MHC molecules.J Biol Chem 267: 11669–11672, 1992
Yewdell, J. W., Esquivel, F., Arnold, D., Spies, T., Eisenlohr, L. C., and Bennink, J. R. Presentation of numerous viral peptides to mouse major histocompatibility complex (MHC) class I-restricted T lymphocytes is mediated by the human MHC-encoded transporter or by a hybrid mouse-human transporter.J Exp Med 177: 1785–1790, 1993
Author information
Authors and Affiliations
Additional information
The nucleotide sequence data reported in this paper have been submitted to the EMBL/GenBank nucleotide sequence databases and have been assigned the accession numbers L49032 (Gogo-TAP2a), L49033 (Gogo-TAP2b), L49034 (Gogo-TAP2c), and L49035 (Gogo-TAP2d)
Rights and permissions
About this article
Cite this article
Loflin, P.T., Laud, P.R., Watkins, D.I. et al. Identification of new TAP2 alleles in gorilla: evolution of the locus within hominoids. Immunogenetics 44, 161–169 (1996). https://doi.org/10.1007/BF02602581
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02602581