Recognition of microbiota-derived N-formyl methionine peptides by non-classical MHC class I, H2-M3-restricted CD8 T cells

A new study in journal Cell revealed that a specialized subset of CD8 T cells recognize conserved microbial derived N-formyl methionine peptides in context of non-classical MHC class I molecule H2-M3.

Using skin commensal Staphylococcus epidermidis (S. epidermidis) challenge model, the authors showed that recognition of this microbe by CD8+ T cells specifically relied on H2-M3 rather than other MHC molecules.

H2-M3 has been known to bind peptides that contain an N-formyl methionine (fMet), which is required to initiate protein translation in bacteria and mitochondria. Indeed, fMet peptide:H2-M3 tetramer (f-MIIINA:H2-M3) could stain a population of CD8 T cells from skin or lymph nodes. Interestingly, half of tetramer positive CD8 T cells were CD44^hi even in germ-free mice indicating cross-reactivity with other antigens or "ready-made" origin similar to thymus-derived Tregs.

To show biological significance of these CD8 T cell population recognizing commensals, the authors used H2-M3 KO mice and wound healing experiment. The authors claim that in the absence of H2-M3 wound healing was delayed, though data do not strongly support such assertion.

In summary, the authors described yet another T cell population recognizing products from bacteria. Because such recognition does not produce inflammation the authors suggest it could be involved in wound repair. But wound repair model provided very minimal support for such hypothesis. Basically, they missed the central point to make this paper relevant. So how it ended up in Cell? Ask editors. I could come up with couple of suggestions. When the paper's authors list includes Giorgio Trinchieri, John O’Shea and senior author, Yasmine Belkaid, all heads of big labs at NIH, it is quite difficult to say no.

posted by David Usharauli