Variable immunodominance hierarchies for H2-M3-restricted N-formyl peptides following bacterial infection

H2-M3-restricted presentation of N-formyl methionine (f-Met) peptides to CD 8(+) T cells provides a mechanism for selective recognition of bacterial in fection. In this report we demonstrate that Listeria monocytogenes infectio n induces distinct CD8(+) T cell populations specific for each of the known Listeria-derived formyl methionine peptides presented by M3. The sum H2-M3 -restricted, Listeria-specific T cell response constitutes a major fraction of the total CD8(+) T cell response to primary infection. H2-M3-restricted T cell populations expand synchronously in vivo and achieve peak frequenci es similar to2 days earlier than MHC class Ia-restricted T cell populations . Although cross-recognition of different f-Met peptides by M3-restricted T cells was previously described, costaining of CD8(+) T cells ex vivo with H2-M3 tetramers complexed with different f-Met peptides shows that the majo rity of Listeria-specific, M3-restricted CD8(+) T cells are peptide specifi c. In contrast to the highly predictable size and immunodominance hierarchi es of MHC class Ia-restricted T cell responses, the magnitudes of T cell re sponses specific for H2-M3-restricted peptides are remarkably variable betw een genetically identical mice. Our Endings demonstrate that H2-M3-restrict ed T cell responses are distinct from classically restricted T cell respons es to bacterial infection.