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Alleles and haplotypes of the MHC-encoded ABC transporters TAP1 and TAP2

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Abstract

TAP1 and TAP2 are two major histocompatibility complex (MHC) genes, located between HLA-DP and -DQ, whose products form a transporter molecule involved in endogenous antigen processing. Polymorphic residues have been described in both genes and, in this study, we have identified another polymorphic site within the adenosine triphosphate (ATP)-binding domain of TAP2. We have used the amplification refractoru mutation system (ARMS) polymerase chain reaction (PCR) to characterize TAP1 and TAP2 alleles and haplotypes in a reference panel of 115 homozygous typing cell lines. Of four possible TAP1 alleles, we observed three, and of eight possible TAP2 alleles, we observed five. Among 88 (homozygous typing cells) (HTCs) homozygous at HLA-DR, -DQ and TP, 80 were also homozygous at TAP1 and TAP2. Of 27 HTCs homozygous at HLA-DR and -DQ, but heterozygous at -DP, 14 were homozygous at TAP1 or TAP2 and 13 heterozygous, consistent with recombination taking place either side of the TAP loci. Of the fifteen possible combinations of TAP1 and TAP2 alleles, we observed eleven, each at a frequency similar to that predicted by individual allele frequencies. In this ethnically heterogeneous panel there is no indication that particular combinations of TAP1 and TAP2 have been maintained together.

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References

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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: 738–41, 1990

    Article  CAS  PubMed  Google Scholar 

  • Higgins, C. F., Hyde, S. C., Mimmack, M. M., Gileadi, U., Gill, D. R., and Gallagher, M. P. Binding protein-dependent transport systems. J Bioenerg Biomembr 22: 571–592, 1990

    Google Scholar 

  • Kelly, A., Powis, S. H., Kerr, L.-A., Mockridge, I., Elliot, 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

    Google Scholar 

  • Kendall, E., Sargent, C. A., and Campbell, R. D. Human major histocompatibility complex contains a new cluster of genes between the HLA-D and complement C4 loci. Nucleic Acids Res 18: 7251–7, 1990

    Google Scholar 

  • Kimura, A., Dong, R.-P., Harada, T., and Sasazuki, T. DNA typing of HLA class II genes in B lymphoblastoid cell lines homozygous for HLA. Tissue Antigens 40: 5–12, 1992

    Google Scholar 

  • Lo, Y.-M. D., Patel, P., Newton, C. R., Markham, A. F., Fleming, K. A., and Wainscoat, J. S. Direct haplotype determination by double ARMS: specificity, sensitivity and genetic applications. Nucleic Acids Res 19: 3561–3567, 1991

    Google Scholar 

  • 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

    Google Scholar 

  • Newton, C. R., Graham, A., Heptinstall, L. E., Powell, S. J., Summers, C., Kalsheker, N., Smith, J. C., and Markham, A. F. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 17: 2503–2516, 1989

    CAS  PubMed  Google Scholar 

  • Parham, P. Flying the first class flag. Nature 357: 193–194, 1992

    Google Scholar 

  • Powis, S. J., Townsend, A. R. M., Deverson, E. V., Bastin, J., Butcher, G. W., and Howard, J. C. Restoration ot antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter. Nature 354: 528–531, 1991

    Google Scholar 

  • 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, 1992a

    Google Scholar 

  • 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, 1992b

    Google Scholar 

  • Robertson, M. Proteasomes in the pathway. Nature 353: 300–301, 1991

    Google Scholar 

  • Safa, A., 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

    Google Scholar 

  • Seed, B. An LFA-3 cDNA encodes a phospholipid membrane protein homologous to its receptor CD2. Nature 329: 840–842, 1987

    Google Scholar 

  • 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: 744–7, 1990

    Google Scholar 

  • Spies, T., Cerundolo, V., Colonna, M., Creswell, P., Townsend, A., and DeMars, R. Presentation of endogenous viral antigens dependent on putative peptide transporter heterodimer. Nature 355: 644–646, 1992

    Google Scholar 

  • 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

    Google Scholar 

  • Tiwari, J. L. and Terasaki, P. I. HLA antigens associated with diseases. In J. L. Tiwaria and P. I. Terasaki (eds.): HLA and Disease Associations, pp. 42–48, Springer, New York, 1985

    Google Scholar 

  • 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: 741–4, 1990

    Google Scholar 

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Correspondence to: S. H. Powis.

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Powis, S.H., Tonks, S., Mockridge, I. et al. Alleles and haplotypes of the MHC-encoded ABC transporters TAP1 and TAP2 . Immunogenetics 37, 373–380 (1993). https://doi.org/10.1007/BF00216802

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  • DOI: https://doi.org/10.1007/BF00216802

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