HLA Matching in Clinical Organ Transplantation

Alloimmune responses are T cell dependent. T cells recognize and are activated by peptides bound to HLA molecules, which are highly polymorphic, cell membrane bound, and equipped with a peptide binding cleft. The polymorphic residues lining the cleft determine which peptides will be bound (Bjorkman et al. 1987). However, HLA molecules do not discriminate between peptide fragments from nonself-(i.e., derived from viruses, bacteria, etc.) or self-proteins, and clefts of most HLA molecules will probably be occupied by endogenous self-peptides.