Beta 2-microglobulin independent presentation of exogenously added foreign peptide and endogenous self-epitope by MHC class I alpha-chain to a cross-reactive CD8+ CTL clone.
CD8+ T cells recognize antigenic peptides in the context of MHC class I molecules that encompass two distinct polypeptide chains, the MHC-encoded alpha-chain and the non-MHC-encoded beta 2-microglobulin (beta 2-m). The beta 2-m is considered essential for the stability and function of the MHC class I peptide complex and, hence, for peptide presentation to CD8+ T cells. In this study, we describe peptide presentation by macrophages from beta 2-m-deficient mice to a CD8+ CTL clone tht cross-recognizes an H-2Db-restricted peptide of the mycobacterial heat shock protein 60 (hsp60) and a self-peptide presented by IFN-gamma-stressed macrophages. Specific lysis of stressed or hsp60 peptide-pulsed beta 2-m-/- macrophages was inhibited by the nucleoprotein peptide with high affinity to H-2Db. Brefeldin A, a known inhibitor of MHC class I processing, interfered with lysis of IFN-gamma-stressed, but not of hsp60 peptide-pulsed, beta 2-m-/- macrophages. The hsp60 peptide failed to stimulate surface expression of H-2Db in beta 2-m-/- macrophages, and slightly increased MHC class I expression in the transporter mutant cell line RMA-S, as detected by cytofluorometry. We concLude that presentation of endogenously processed cytosolic epitopes and exogenously added foreign peptides by the MHC class I alpha-chain can occur independent from beta 2-m. Presumably, H-2Db peptides, but not H-2Kb peptides, have the capacity to induce and/or stabilize surface expression of a small number of MHC class I alpha-chains, and this low density is sufficient for recognition by CD8+ CTL, although it need not be detected by serologic means.
Zügel
U
U
Department of Immunology, University of Ulm, Germany.
Schoel
B
B
Kaufmann
S H
SH
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D001324:Autoantigens / Q000276:immunology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D001613:beta 2-Microglobulin / Q000502:physiology*
D001324:Autoantigens; D018834:Chaperonin 60; D000939:Epitopes; D006183:H-2 Antigens; D010455:Peptides; D001613:beta 2-Microglobulin