PMID: 7538543Jun 1, 1995Paper

An epitope-selective, transporter associated with antigen presentation (TAP)-1/2-independent pathway and a more general TAP-1/2-dependent antigen-processing pathway allow recognition of the HIV-1 envelope glycoprotein by CD8+ CTL

The Journal of Immunology : Official Journal of the American Association of Immunologists
S A HammondR F Siliciano

Abstract

The lysis of virally infected cells by CTLs requires the recognition of processed fragments of viral proteins presented in association with class I MHC molecules on the surfaces of infected cells. Processing begins in the cytosol with the degradation of viral proteins into peptides that are then transported into the endoplasmic reticulum (ER) for association with newly synthesized class I molecules. Transport is mediated by a heterodimer of the MHC-encoded proteins, transporter associated with Ag presentation (TAP)-1 and TAP-2. Uncertainty exists over the site of processing of viral envelope (env) proteins. The extracellular domains of env proteins are not present in the cytosol, the site in which the class I-restricted Ag-processing pathway begins. Rather, the ecto-domains of env proteins are cotranslationally translocated into the ER during biosynthesis. We have analyzed the processing of the HIV-1 env protein by using a large series of env-specific human CD8+ CTL clones. These studies have led to the delineation of two distinct processing pathways. The first pathway permits a subset of class I-restricted epitopes in the ecto-domain of the env protein to be generated efficiently by a TAP-1/2-independent mechanism localized to...Continue Reading

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