Antimicrobial activity of MHC class I-restricted CD8+T cells in human tuberculosis

Studies of mouse models of tuberculosis (TB) infection have indicated a cen tral role for MHC class I-restricted CD8+ T cells in protective immunity. T o define antigens and epitopes of Mycobacterium tuberculosis (MTB) proteins that are presented by infected cells to CD8+ T cells, we screened 40 MTB p roteins for HLA class I A*0201-binding motifs, Peptides that bound with hig h affinity to purified HLA molecules were subsequently analyzed for recogni tion by CD8+ cytotoxic T lymphocytes, We identified three epitopes recogniz ed by CD8+ T cells from patients recovering from TB infection. Those three epitopes were derived from three different antigens: thymidylate synthase ( ThyA(30-38)). RNA polymerase beta -subunit (RpoB(127-135)), and a putative phosphate transport system permease protein A-1 (PstA1(75-83)) In addition, CD8+ T cell lines specific for three peptides (ThyA(30-38). PstA1(75-83), and 85B(15-23)) were generated from peripheral blood mononuclear cells of n ormal HLA-A*0201 donors. These CD8+ T cell lines specifically recognized MT B-infected macrophages, as demonstrated by production of IFN-gamma and lysi s of the infected target cells. Finally, CD8+ cytbtdxic:T lymphocytes reduc ed the viability of the intracellular MTB, providing evidence that CD8+ T c ell recognition of MHC class I-restricted epitopes of these MTB antigens ca n contribute to effective immunity against the pathogen.