Presenting the Alternatives

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Science  08 Jun 2001:
Vol. 292, Issue 5523, pp. 1799
DOI: 10.1126/science.292.5523.1799d

Studies using experimental infection models of Mycobacterium tuberculosis, the agent that causes tuberculosis, suggest that CD8+ T cells may play an important role in controlling this disease. However, the non-cytosolic location of this bacterium within infected macrophages impedes presentation of epitopes via the class I major histocompatibility complex (MHC) pathway. Thus, nonclassical pathways of presentation have been implicated in immune recognition of M. tuberculosis.

Chun et al. describe the participation of a new category of nonclassically restricted peptides in T cell recognition of M. tuberculosis. Candidates were identified by screening the bacterial genome for sequences exhibiting identity with N-formylated peptides already known to bind preferentially to the murine nonclassical MHC class Ib protein, H2-M3. Several of the identified peptides induced H2-M3 restricted CD8+ cytotoxic lymphocyte (CTL) responses after priming in vivo. These CTLs could lyse infected macrophages, as well as peptide-loaded target cells, and also were present in mice infected with M. tuberculosis. Identification of similar pathways of N-formyl peptide presentation in humans might prove useful in the development of new vaccines. — SJS

J. Exp. Med.193, 1213 (2001).

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