Activation of human CD8(+) alpha beta TCR+ cells by Mycobacterium tuberculosis via an alternate class I MHC antigen-processing pathway

Human immune responses to M, tuberculosis are characterized by activation o f multiple T cell subsets including CD4(+), CD8(+), and gamma delta T cells , and the role of CD8(+) alpha beta TCR+ T cells in this response is poorly understood. Stimulation of T cells from healthy tuberculin skin test-posit ive persons with live M, tuberculosis-H37Ra or soluble M, tuberculosis Ags readily up-regulated IL-2R alpha (CD25) expression on CDS' T cells. Purifie d resting and activated CD8(+) T cells produced IFN-gamma and proliferated to both M, tuberculosis bacilli and soluble mycobacterial Ags with monocyte s as APC, Precursor frequency of mycobacterial Ag-specific CD8(+) T cells b y IFN-gamma enzyme-linked immunospot was 5-10-fold lower than the precursor frequency of CD4(+) T cells, and IFN-gamma secretion by CD8(+) T cells was 50-100-fold lower. CD8(+) T cells secreted similar to 10-fold less IFN-gam ma per cell than CD4(+) T cells in response to mycobacterial Ags, CD8(+) T cell responses to M, tuberculosis bacilli were blocked by anti-MHC class I antibody and required Ag processing. Processing of M, tuberculosis bacilli by monocytes for presentation to MHC class I-restricted CD8(+) T cells was insensitive to brefeldin A treatment, which blocks the conventional MHC cla ss I Ag-processing pathway. These results represent the first demonstration that human tells can process pathogen Ags via an alternate Ag-processing p athway for MHC class I and suggest a mechanism for participation of IFN-gam ma-secreting CD8(+) T cells in the human immune responses to M, tuberculosi s.