T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides

TY - JOUR

T1 - T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides

AU - Larsen, S L

AU - Pedersen, L O

AU - Buus, S

AU - Stryhn, A

N1 - Keywords: Amino Acid Sequence; Animals; Antigen-Presenting Cells; Antigens, CD13; Histocompatibility Antigens Class II; Hybridomas; Lymphocyte Activation; Mice; Molecular Sequence Data; Muramidase; Peptides; T-Lymphocytes; Tumor Cells, Cultured

PY - 1996

Y1 - 1996

N2 - Endocytosed protein antigens are believed to be fragmented in what appears to be a balance between proteolysis and MHC-mediated epitope protection, and the resulting peptide-MHC complexes are transported to the surface of the antigen-presenting cells (APC) and presented to T cells. The events that lead to antigenic peptide generation and the compartments where antigen processing takes place remains somewhat enigmatic. The importance of intracellular antigen processing has been well established; 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 inhibitors to demonstrate that the APC surface has a considerable potential for antigen processing. Specific antibodies further identified the exopeptidase Aminopeptidase N (APN, CD13) as one of the enzymes involved in the observed cell-surface antigen processing. The NH2-terminal end of the longer peptide could, even while bound to major histocompatibility complex (MHC) class II molecules, be digested by APN with dramatic consequences for T cell antigen recognition. This could be demonstrated both in cell-free systems using purified reagents and in cellular systems. Thus, MHC class II and APN may act in concert to generate the final T cell epitopes.

AB - Endocytosed protein antigens are believed to be fragmented in what appears to be a balance between proteolysis and MHC-mediated epitope protection, and the resulting peptide-MHC complexes are transported to the surface of the antigen-presenting cells (APC) and presented to T cells. The events that lead to antigenic peptide generation and the compartments where antigen processing takes place remains somewhat enigmatic. The importance of intracellular antigen processing has been well established; 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 inhibitors to demonstrate that the APC surface has a considerable potential for antigen processing. Specific antibodies further identified the exopeptidase Aminopeptidase N (APN, CD13) as one of the enzymes involved in the observed cell-surface antigen processing. The NH2-terminal end of the longer peptide could, even while bound to major histocompatibility complex (MHC) class II molecules, be digested by APN with dramatic consequences for T cell antigen recognition. This could be demonstrated both in cell-free systems using purified reagents and in cellular systems. Thus, MHC class II and APN may act in concert to generate the final T cell epitopes.

M3 - Journal article

C2 - 8691132

SN - 0022-1007

VL - 184

SP - 183

EP - 189

JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

IS - 1

ER -