Sl. Larsen et al., T-CELL RESPONSES AFFECTED BY AMINOPEPTIDASE-N (CD13)-MEDIATED TRIMMING OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-BOUND PEPTIDES, The Journal of experimental medicine, 184(1), 1996, pp. 183-189
Endocytosed protein antigens are believed to be fragmented in what app
ears to be a balance between proteolysis and MHC-mediated epitope prot
ection, and the resulting peptide-MHC complexes are transported to the
surface of the antigen-presenting cells (APC) and presented to T cell
s. The events that lead to antigenic peptide generation and the compar
tments where antigen processing takes place remains somewhat enigmatic
. The importance of intracellular antigen processing has been well est
ablished; however, it is unclear whether additional processing occurs
at the APC surface. To follow antigen processing, we have identified a
pair of T cell hybridomas that recognize. a long vs. a short version
of the same epitope. We have used prefixed APC and various protease in
hibitors to demonstate that the APC surface has a considerable potenti
al for antigen processing. Specific antibodies further identified the
exopeptidase Aminopeptidase N (APN, CD13) as one of the enzymes involv
ed in the observed cell-surface antigen processing. The NH2-terminal e
nd of the longer peptide could, even while bound to major histocompati
bility complex (MHC) class II molecules, be digested by APN with drama
tic consequences for T cell antigen recognition. This could be demonst
rated both in cell-free systems using purified reagents and in cellula
r systems. Thus, MHC class II and APN may act in concert to generate t
he final T cell epitopes.