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Polymorphic peptide transporters in MHC class I monomorphic Syrian hamster

M Lobigs1, H S Rothenfluh, R V Blanden

  • 1Division of Cell Biology, John Curtin School of Medical Research, Australian National University, P. O. Box 334, Canberra, ACT 2601, Australia.

Immunogenetics
|January 1, 1995
PubMed
Summary

Syrian hamster cell lines show functional differences in peptide transporters (TAP1 and TAP2), unlike polymorphic species like humans and mice. This suggests functional polymorphism in hamster antigen presentation machinery.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Major histocompatibility complex (MHC) class I molecules present peptides to T cells.
  • Species with highly polymorphic MHC class I (human, mouse) lack detectable functional polymorphism in TAP1 and TAP2 peptide transporters.
  • Syrian hamsters have monomorphic MHC class I, making them a model to study antigen presentation machinery.

Purpose of the Study:

  • To investigate the antigen-presentation machinery in Syrian hamsters.
  • To determine if Syrian hamster cell lines exhibit functional polymorphism in peptide transporters (TAP1 and TAP2).

Main Methods:

  • Expression of mouse MHC class I molecules (H2 Kk, Kd, Kb, Dd) in Syrian hamster cell lines using recombinant vaccinia viruses (VV).
  • Analysis of VV peptide presentation to cytotoxic T (Tc) cells.

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  • Fluorescence-activated cell sorter (FACS) analysis.
  • Cloning and sequencing of the Syrian hamster TAP2 gene.

    • Main Results:

    • Four hamster cell lines (HaK, FF, MF-2, HT-1) showed no defect in expressing H2 class I molecules and VV peptides.
    • Two cell lines (BHK-21, NIL-2) showed defects in expressing Kk and Kd, but not Dd and Kb.
    • Surface expression of Kk and Kd in BHK-21 and NIL-2 cells was restored upon superinfection with VV encoding rat TAP1 and TAP2.
    • Sequencing revealed 78-87% similarity between Syrian hamster TAP2 and human, mouse, and rat TAP2 sequences.

    Conclusions:

    • Syrian hamster cell lines exhibit functionally polymorphic peptide transporters (TAP1 and TAP2).
    • This functional polymorphism in peptide transporters contributes to the antigen presentation machinery in Syrian hamsters.
    • The TAP2 gene sequence is conserved across species, despite functional differences observed in hamsters.