Polymorphic peptide transporters in MHC class I monomorphic Syrian hamster

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.
• 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.