Target Discovery and Validation Reviews and Protocols

294 Sioud
Fig. 8. Schematic of class I pathway of antigen processing. The proteasome digests
endogenous cellular proteins into peptide fragments that are transported to the endoplasmic
reticulum where they will be taken up by major histocompatability complex
(MHC) I molecules. Subsequently, the complexes are delivered to the cell surface. TAP,
transporter associated with antigen presentation.
posttranslational modifications), naive T-cell interaction with self-peptides may
trigger their full activation, thereby inducing autoimmunity. This type of reactivity
may benefit patients with cancers. Another question is whether B-cells, as T-cells,
interact with self for survival. In this respect, all peripheral B-cells fail to be maintained
when the BCR is deleted, indicating that BCR signaling also is required for
B-cell survival (24). Again, the strength of BCR signaling seems to be a major
player in peripheral B-cell fate. Therefore, the data predict that both T- and B-cells
must interact with self-antigens to survive.
6. Antigen Processing
6.1. Class I Pathway of Antigen Processing
The TCR recognizes antigen only when it is displayed on the surface of the
target cell as peptide fragment by the class I and class II molecules of the MHC.
Class I molecules are present on virtually all nucleated cells and predominantly
present peptides derived from endogenous proteins as illustrated in Fig. 8. These