What Is Direct Allorecognition?

Direct allorecognition is the process by which
donor-derived major histocompatibility complex (MHC)-peptide
complexes, typically presented by donor-derived ‘passenger’
dendritic cells, are recognised directly by recipient T cells.
In this review, we discuss the two principle theories which
have been proposed to explain why individuals possess a
high-precursor frequency of T cells with direct allospecificity
and how self-restricted T cells recognise allogeneic MHCpeptide
complexes. These theories, both of which are supported
by functional and structural data, suggest that T cells
recognising allogeneic MHC-peptide complexes focus either
on the allopeptides bound to the allo-MHC molecules or the
allo-MHC molecules themselves. We discuss how direct
alloimmune responses may be sustained long term, the consequences
of this for graft outcome and highlight novel strategies
which are currently being investigated as a potential
means of reducing rejection mediated through this pathway.