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 clas s I molecules that encompass two distinct polypeptide chains, the MHC- encoded alpha-chain and the non-MHC-encoded beta(2)-microglobulin (bet a(2)-m). The beta(2)-m is considered essential for the stability and f unction of the MHC class I peptide complex and, hence, for peptide pre sentation to CD8(+) T cells. In this study, we describe peptide presen tation by macrophages from beta(2)-m-deficient mice to a CD8(+) CTL cl one that cross-recognizes an H-2D(b)-restricted peptide of the mycobac terial heat shock protein 60 (hsp60) and a self-peptide presented by I FN-gamma-stressed macrophages. Specific lysis of stressed or hsp60 pep tide-pulsed beta(2)-m(-/-) macrophages was inhibited by the nucleoprot ein peptide with high affinity to H-2D(b). Brefeldin A, a known inhibi tor of MHC class I processing, interfered with lysis of IFN-gamma-stre ssed, but not of hsp60 peptide-pulsed, beta(2)-m(-/-) macrophages. The hsp60 peptide failed to stimulate surface expression of H-2D(b) in be ta(2)-m(-/-) macrophages, and slightly increased MHC class I expressio n in the transporter mutant cell line RMA-S, as detected by cytofluoro metry. We conclude that presentation of endogenously processed cytosol ic epitopes and exogenously added foreign peptides by the MHC class I alpha-chain can occur independent from beta(2)-m Presumably, H-2D(b) p eptides, but not H-2K(b) peptides, have the capacity to induce and/or stabilize surface expression of a small number of MHC class I alpha-ch ains, and this low density is sufficient for recognition by CD8(+) CTL , although it need not be detected by serologic means.