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T-Cell Stimulating Antigen Genes in Tumor Cells

Institution: University of California, Berkeley
Investigator(s): Nilabh Shastri, Ph.D.
Award Cycle: 1994 (Cycle 3) Grant #: 3RT-0289 Award: $362,814
Subject Area: Cancer
Award Type: Research Project Awards

Initial Award Abstract
This project aims to identify the antigen genes that are expressed in normal as well as tumor cells and are recognized by T-cells as peptide/MHC complexes. We are identifying and isolating these genes using our unique expression cloning strategies for both CD4+ and CD8+ T-cell defined antigens. Towards this end we have generated a panel of lacZ inducible T cell hybrids that recognize unknown antigens expressed by B6 spleen cells, mouse tumors and the bacterial pathogen listeria monocytogenes. With two of these T-cells (bmlBZ19.4, and LMZ30.4) used as a single cell probes, we have isolated a cDNA clone from mouse B6 spleen cell and listeria monocytogenes DNA libraries respectively. These results have established expression cloning strategies for identifying unknown T-cell stimulating antigens and have provided knowledge of the peptides and their donor proteins that elicit T-cell immunity. We are currently extending these results to identify the unknown antigen genes recognized by the other T-cells in our panel. We expect the results will allow us to (a) establish the protein sources for peptide/MHC complex expressed on the antigen presenting cell surface, (b) determine the role of these antigenic peptides in the induction of specific T-cell immunity.

LacZ inducible, antigen/MHC specific T-cell hybrids
Periodical: International Immunology Index Medicus:
Authors: Sanderson S, Shastri N ART
Yr: 1994 Vol: 6 Nbr: 3 Abs: Pg: 369-376

Expression of endogenous peptide/MHC class II complexes derived from invariant chain/antigen fusion proteins
Periodical: Proceedings of the National Academy of Sciences of the United States of America Index Medicus:
Authors: Sanderson S, Frauwirth K, Shastri N ART
Yr: 1995 Vol: 92 Nbr: 16 Abs: Pg: 7217-7221

Presentation without processing of endogenous precursors in the MHC class I antigen processing pathway
Periodical: Journal of Biological Chemistry Index Medicus:
Authors: Buchholz D, Scott P, Shastri N ART
Yr: 1995 Vol: 270 Nbr: 12 Abs: Pg: 6515-6522

Major histocompatibility class I molecules present cryptic translation products to T-cells
Periodical: Journal of Biological Chemistry Index Medicus:
Authors: Shastri N, Nguyen V, Gonzalez F ART
Yr: 1995 Vol: 270 Nbr: 3 Abs: Pg: 1088-1091

The roles of MHC class I molecules in the generation of endogenous peptide/MHC complexes
Periodical: Journal of Immunology Index Medicus:
Authors: Malarkannan S, Goth S, Buchholz DR, Shastri N ART
Yr: 1995 Vol: 154 Nbr: 12 Abs: Pg: 585-598

Single T-cell probes for antigen/MHC expression
Periodical: Current Opinion in Immunology Index Medicus:
Authors: Shastri N ART
Yr: 1995 Vol: 7 Nbr: 2 Abs: Pg: 258-262