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Open reading frame sequencing and structure-based alignment of polypeptides encoded by RT1-Bb, RT1-Ba, RT1-Db, and RT1-Da alleles

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Abstract

MHC class II genes are major genetic components in rats developing autoimmunity. The majority of rat MHC class II sequencing has focused on exon 2, which forms the first external domain. Sequence of the complete open reading frame for rat MHC class II haplotypes and structure-based alignment is lacking. Herein, the complete open reading frame for RT1-Bβ, RT1-Bα, RT1-Dβ, and RT1-Dα was sequenced from ten different rat strains, covering eight serological haplotypes, namely a, b, c, d, k, l, n, and u. Each serological haplotype was unique at the nucleotide level of the sequenced RT1-B/D region. Within individual genes, the number of alleles identified was seven, seven, six, and three and the degree of amino-acid polymorphism between allotypes for each gene was 22%, 16%, 19%, and 0.4% for RT1-Bβ, RT1-Bα, RT1-Dβ, and RT1-Dα, respectively. The extent and distribution of amino-acid polymorphism was comparable with mouse and human MHC class II. Structure-based alignment identified the β65–66 deletion, the β84a insertion, the α9a insertion, and the α1a–1c insertion in RT1-B previously described for H2-A. Rat allele-specific deletions were found at RT1-Bα76 and RT1-Dβ90–92. The mature RT1-Dβ polypeptide was one amino acid longer than HLA-DRB1 due to the position of the predicted signal peptide cleavage site. These data are important to a comprehensive understanding of MHC class II structure-function and for mechanistic studies of rat models of autoimmunity.

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Acknowledgements

This work was supported by an American Diabetes Association Junior Faculty Award to Ruth Ettinger (1-02-JF-06) and in part by the National Institutes of Health (PO1 AI42380). The authors thank Dr Åke Lernmark and Dr George K. Papadopoulos for helpful discussions and for critically reviewing the manuscript. All experiments complied with the current laws of the United States of America.

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  1. Antonis K. Moustakas

    Present address: Department of Biological Agriculture, Technological Educational Institute of Ionian Islands, Argostoli, Kefalonia, Greece

Authors and Affiliations

  1. Robert H. Williams Lab, Department of Immunology, University of Washington, Box 357710, 1959 NE Pacific St, HSB K-165, Seattle, WA, 98195-7710, USA

    Ruth A. Ettinger & Suzanne D. Lobaton

  2. Laboratory of Biochemistry and Biophysics, Faculty of Agricultural Technology, Technological Educational Institute of Epirus, 47100, Arta, Greece

    Antonis K. Moustakas

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  1. Ruth A. Ettinger
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Correspondence to Ruth A. Ettinger.

Additional information

Nucleotide sequence data reported are available in the GenBank database under the accession numbers AY626180–AY626189 for all RT1-Bb sequences, AY626190–AY626199 for all RT1-Ba sequences, AY626200-AY626209 for all RT1-Db sequences and AY626210–AY626219 for all RT1-Da sequences.

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Ettinger, R.A., Moustakas, A.K. & Lobaton, S.D. Open reading frame sequencing and structure-based alignment of polypeptides encoded by RT1-Bb, RT1-Ba, RT1-Db, and RT1-Da alleles. Immunogenetics 56, 585–596 (2004). https://doi.org/10.1007/s00251-004-0725-7

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