Specificity of T-cell alloreactivity

A high frequency of T cells are alloreactive and are involved in transplant rejection and graft-versus-host disease (GVHD).Many alloreactive T cells are much more peptide specific than previously thought, and few if any recognize only the MHC molecule.Alloreactive T cells are polyspecific, being able to recognize multiple distinct peptide–MHC complexes. This provides a potential explanation for the high frequency of allorecognition.Structural studies of T-cell receptor (TCR)–peptide–MHC complexes reveal that alloreactive TCRs bind to peptide–MHC molecules in conventional ways and appear to exhibit similar diverse binding modes as conventional T cells.There is no single set of molecular interactions that reveals a germline-encoded preference of TCRs to bind MHC molecules, but there may be conserved contacts that differ for each TCR variable (V) region and MHC allele.Histocompatibility responses are important for marine colonial tunicates, allowing them to reject parasitic stem cells, but there is no selective advantage for alloreactivity in vertebrates. For vertebrates, alloreactivity may simply be the consequence of an inherent affinity of the TCR for the MHC molecule and a conserved surface among MHC alleles.