Antigen processing by endosomal proteases determines which sites of sperm-whale myoglobin are eventually recognized by T cells
✍ Scribed by Johannes M. Van Noort; Jacqueline Boon; Alfons C. M. Van der Drift; Josée P. A. Wagenaar; Annemieke M. H. Boots; Claire J. P. Boog
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 1003 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Antigen processing by endosomal proteases determines which sites of sperm-whale myoglobin are eventually recognized by Tcells
This study reports an identification of the major processing products of an exogenous protein antigen, viz. sperm-whale myoglobin, as obtained after cell-free processing with partially purified macrophage endosomes. It is demonstrated that such a system yields fragments that are indistinguishable by high performance liquid chromatography analysis from those generated after uptake of myoglobin inside live macrophages. The concerted action of the endosomal proteases cathepsin D and cathepsin B can account for nearly all cleavages observed. Cathepsin D appears to be mainly responsible for the initial cleavage of myoglobin, while cathepsin B catalyzes the C-terminal trimming of initially released fragments. The fragments released by cathepsin D contain most, if not all, major epitopes for murine myoglobinspecific helper T cells. Interestingly, each known T cell epitope of myoglobin is located at the very N terminus of a different myoglobin fragment released upon processing. In order to explain this correspondence, noted also in several other protein antigens, a structural relationship is proposed between antigen processing by cathepsin D and antigen recognition by major histocompatibility complex (MHC) class II products. As is demonstrated here, this relationship may be used as a predictive tool for the identification of MHC-binding sequences as well as of T cell epitopes in their naturally occurring form.