Sensitization of MHC class I-restricted T cells to exogenous proteins: evidence for an alternative class I-restricted antigen presentation pathway.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Sensitization of MHC class I-restricted T cells to exogenous proteins: evidence for an alternative class I-restricted antigen presentation pathway.

Immunology. 1995 Oct;86(2):287-95. Unique Identifier : AIDSLINE MED/96096250
Martinez-Kinader B; Lipford GB; Wagner H; Heeg K; Institute for Medical Microbiology and Hygiene, Technical; University of Munich, Germany.

Abstract: Immunization with exogenous proteins usually fails to immunize CD8+ T cells in vivo. Here we report that chicken ovalbumin (OVA) denatured by heat or sodium dodecyl sulphate (SDS) effectively induced CD8+ cytolytic T cells in vivo. The cytolytic T-lymphocyte (CTL) population generated recognized syngeneic target cells pulsed with the immunodominant OVA peptide (257-264) or transfected with the OVA protein-encoding gene. To analyse the mechanisms of how denatured OVA enters the class I-restricted pathway of antigen presentation, we took advantage of the fact that denatured OVA sensitizes target cells in vitro for lysis by OVA-specific CTL. We found that neither inhibition of protein synthesis (by cycloheximide) nor blocking of transport via the Golgi apparatus (by brefeldin A) interfered with the class I-restricted presentation of denatured OVA in vitro. In addition, transporter associated with antigen presentation (TAP)-dependent transport into the endoplasmic reticulum (ER) was not required for effective presentation, as TAP-deficient cells (RMA-S) could be sensitized effectively by denatured OVA for recognition by class I-restricted CTL. In contrast, class I-restricted presentation of denatured OVA was sensitive to lysosomotropic agents (NH4Cl, vinblastine and leupeptin), indicating that endosomal-like compartments are involved in the presentation of denatured OVA. Sensitization was inhibited at low temperature, yet took place in the presence of sucrose and in the absence of K+, indicating that denatured OVA enters the cell via fluid-phase endocytosis. Hence the results provide further evidence for an alternative class I-restricted pathway of antigen presentation for exogenous proteins. As that pathway seems to be effective in vivo, it offers a new and effective way of vaccination of CD8+ CTL.

Keywords: Amino Acid Sequence Animal Antigen Presentation/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Endocytosis/IMMUNOLOGY Female Heat Histocompatibility Antigens Class I/*IMMUNOLOGY Lysosomes/IMMUNOLOGY Mice Mice, Inbred C57BL Molecular Sequence Data Ovalbumin/*IMMUNOLOGY Protein Denaturation Sodium Dodecyl Sulfate Support, Non-U.S. Gov't JOURNAL ARTICLE
960330
M9630696

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1996. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1996. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .