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Surface expression of the majority of class I major histocompatibility complex (MHC) heavy chains is known to require assembly with beta 2 microglobulin (beta 2m). To define other factors involved in class I MHC assembly, we have studied two tumor cell lines that are deficient in cell surface class I (H-2) expression. The BC2 fibrosarcoma and the CMT lung carcinoma express only intracellular unassociated heavy chains despite the presence of beta 2m. As described previously, when these cell lines are treated with interferon-gamma (IFN-gamma), they are capable of assembling and transporting class I molecules to the cell surface. In this study, we have shown that in the absence of IFN-gamma these mutant cells are unable to present intracellular viral antigens, although they can be lysed by specific cytotoxic T lymphocyte (CTL) after pre-incubation with the corresponding synthetic peptide. Flow cytometric analysis demonstrated that extracellular peptide was capable of increasing twofold the surface expression of beta 2m-heavy chain complexes. Furthermore, immunoprecipitation experiments confirmed that peptide stabilizes chain association in the BC2 cell lysates. However, infecting these mutants with vectors expressing either pre-processed antigen or rapidly degraded antigen, failed to overcome their defect in the presentation of endogenous peptide to specific CTL or to mediate surface expression of class I MHC. Preincubation with IFN-gamma completely reversed the endogenous peptide presentation defect, even in mutant cells transfected with a vector encoding a cDNA for the H-2 molecule restricting CTL recognition. This last result suggests that IFN-gamma corrects the defect by a mechanism separate from simple enhancement of the number of class I molecules produced by the cell. Because there is growing evidence that endogenous peptides can participate in class I MHC assembly, the defect in these mutants could be ascribed to the lack of access to class I molecules by the endogenous peptide. This would prevent stable association of the heavy and light chains and their subsequent transport. Our data suggests that IFN-gamma reestablishes class I MHC surface expression by restoring access of endogenously synthesized peptide to class I molecules.

Original publication

DOI

10.1002/eji.1830220222

Type

Journal article

Journal

Eur J Immunol

Publication Date

02/1992

Volume

22

Pages

433 - 440

Keywords

Amino Acid Sequence, Animals, Antigen-Presenting Cells, Antigens, Viral, Cell Compartmentation, Clone Cells, H-2 Antigens, In Vitro Techniques, Interferon-gamma, Macromolecular Substances, Major Histocompatibility Complex, Mice, Molecular Sequence Data, Peptides, Tumor Cells, Cultured