Extracellular processing and presentation of a 69-mer synthetic polypeptide to MHC class I-restricted T cells

The classical pathway for MHC class-I-restricted Ag presentation processes cytosolic AE synthesized in or delivered into the cytosol for binding to MH C class I molecules in the ER. Alternatively, Ag may be processed and bind class I molecules in endocytic compartments or at the cell surface after re gurgitation of processed peptides. We show that a 69-mer synthetic polypept ide that carries the optimal 9-mer Kd-restricted epitope from the Plasmodiu m berghei circumsporozoite protein, PbCS 245-253, is presented to CD8(+) T cells after a short incubation (1-2 h) with target cells. The presentation kinetics correlate with the length of the peptides when shorter peptide ana logues are used. This presentation is independent of the transporters assoc iated with antigen processing and presentation (TAP), does not require newl y synthesized proteins and does not proceed via regurgitation of intracellu larly processed peptides. In contrast, it is substantially decreased in the absence of beta 2 microglobulin or serum. Taken together, these data sugge st that serum components, such as proteases and beta 2 microglobulin, allow the processing and loading of exogenous polypeptides onto empty cell surfa ce class I molecules for presentation to CTL. (C) 1999 Elsevier Science Ltd . All rights reserved.